American Journal of Ophthalmology

Glaucoma Filtration Surgery: Trabeculectomy or Tube Shunt?

Ronald L. Gross — 2012-05-01

When confronted with the glaucoma patient requiring surgical intervention for filtration, the decision between selecting guarded filtration surgery (trabeculectomy) or an aqueous shunting device (tube shunt) is controversial. Trabeculectomy is the most common procedure selected, although the number performed is decreasing. In contrast, the number of tube shunts performed is increasing, but these remain much less frequent than trabeculectomy. Until the Tube Versus Trabeculectomy Study (TVT), there was little information comparing the 2 procedures. Previous publications have reported the design and 1-year and 3-year results. With the publication of the 2 articles describing the 5-year results concerning treatment outcomes and complications, there are now long-term, high-level data comparing these 2 procedures in glaucoma patients. This commentary discusses the possible implications of the TVT in clinical practice.

Treatment Outcomes in the Tube Versus Trabeculectomy (TVT) Study After Five Years of Follow-up

2012-01-16

Purpose: To report 5-year treatment outcomes in the Tube Versus Trabeculectomy (TVT) Study. Design: Multicenter randomized clinical trial. Methods: Settings: Seventeen clinical centers. Study population: Patients 18 to 85 years of age who had previous trabeculectomy and/or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with intraocular pressure (IOP) ≥18 mm Hg and ≤40 mm Hg on maximum tolerated medical therapy. Interventions: Tube shunt (350-mm2 Baerveldt glaucoma implant) or trabeculectomy with mitomycin C ([MMC]; 0.4 mg/mL for 4 minutes). Main outcome measures: IOP, visual acuity, use of supplemental medical therapy, and failure (IOP >21 mm Hg or not reduced by 20%, IOP ≤5 mm Hg, reoperation for glaucoma, or loss of light perception vision). Results: A total of 212 eyes of 212 patients were enrolled, including 107 in the tube group and 105 in the trabeculectomy group. At 5 years, IOP (mean ± SD) was 14.4 ± 6.9 mm Hg in the tube group and 12.6 ± 5.9 mm Hg in the trabeculectomy group (P = .12). The number of glaucoma medications (mean ± SD) was 1.4 ± 1.3 in the tube group and 1.2 ± 1.5 in the trabeculectomy group (P = .23). The cumulative probability of failure during 5 years of follow-up was 29.8% in the tube group and 46.9% in the trabeculectomy group (P = .002; hazard ratio = 2.15; 95% confidence interval = 1.30 to 3.56). The rate of reoperation for glaucoma was 9% in the tube group and 29% in the trabeculectomy group (P = .025). Conclusions: Tube shunt surgery had a higher success rate compared to trabeculectomy with MMC during 5 years of follow-up in the TVT Study. Both procedures were associated with similar IOP reduction and use of supplemental medical therapy at 5 years. Additional glaucoma surgery was needed more frequently after trabeculectomy with MMC than tube shunt placement.

Postoperative Complications in the Tube Versus Trabeculectomy (TVT) Study During Five Years of Follow-up

2012-01-16

Purpose: To describe postoperative complications encountered in the Tube Versus Trabeculectomy (TVT) Study during 5 years of follow-up. Design: Multicenter randomized clinical trial. Methods: settings: Seventeen clinical centers. study population: Patients 18 to 85 years of age who had previous trabeculectomy and/or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with intraocular pressure (IOP) ≥18 mm Hg and ≤40 mm Hg on maximum tolerated medical therapy. interventions: Tube shunt (350-mm2 Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (MMC 0.4 mg/mL for 4 minutes). main outcome measures: Surgical complications, reoperations for complications, visual acuity, and cataract progression. Results: Early postoperative complications occurred in 22 patients (21%) in the tube group and 39 patients (37%) in the trabeculectomy group (P = .012). Late postoperative complications developed in 36 patients (34%) in the tube group and 38 patients (36%) in the trabeculectomy group during 5 years of follow-up (P = .81). The rate of reoperation for complications was 22% in the tube group and 18% in the trabeculectomy group (P = .29). Cataract extraction was performed in 13 phakic eyes (54%) in the tube group and 9 phakic eyes (43%) in the trabeculectomy group (P = .43). Conclusions: A large number of surgical complications were observed in the TVT Study, but most were transient and self-limited. The incidence of early postoperative complications was higher following trabeculectomy with MMC than tube shunt surgery. The rates of late postoperative complications, reoperation for complications, and cataract extraction were similar with both surgical procedures after 5 years of follow-up.

Diagnostic Capability of Spectral-Domain Optical Coherence Tomography for Glaucoma

Huijuan Wu, Johannes F. de Boer, Teresa C. Chen — 2012-01-20

Purpose: To determine the diagnostic capability of spectral-domain optical coherence tomography in glaucoma patients with visual field defects. Design: Prospective, cross-sectional study. Methods: settings: Participants were recruited from a university hospital clinic. study population: One eye of 85 normal subjects and 61 glaucoma patients with average visual field mean deviation of −9.61 ± 8.76 dB was selected randomly for the study. A subgroup of the glaucoma patients with early visual field defects was calculated separately. observation procedures: Spectralis optical coherence tomography (Heidelberg Engineering, Inc) circular scans were performed to obtain peripapillary retinal nerve fiber layer (RNFL) thicknesses. The RNFL diagnostic parameters based on the normative database were used alone or in combination for identifying glaucomatous RNFL thinning. main outcome measures: To evaluate diagnostic performance, calculations included areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. Results: Overall RNFL thickness had the highest area under the receiver operating characteristic curve values: 0.952 for all patients and 0.895 for the early glaucoma subgroup. For all patients, the highest sensitivity (98.4%; 95% confidence interval, 96.3% to 100%) was achieved by using 2 criteria: ≥ 1 RNFL sectors being abnormal at the < 5% level and overall classification of borderline or outside normal limits, with specificities of 88.9% (95% confidence interval, 84.0% to 94.0%) and 87.1% (95% confidence interval, 81.6% to 92.5%), respectively, for these 2 criteria. Conclusions: Statistical parameters for evaluating the diagnostic performance of the Spectralis spectral-domain optical coherence tomography were good for early perimetric glaucoma and were excellent for moderately advanced perimetric glaucoma.

Use of Topiramate and Risk of Glaucoma: A Case-Control Study

Mahyar Etminan, David Maberley, Frederick S. Mikelberg — 2012-01-20

Purpose: To examine the possible link of acute-onset glaucoma with topiramate. Design: Case-control study. Methods: A case-control study was conducted among a cohort of subjects who had visited an ophthalmologist in the Province of British Columbia, Canada from 2000 to 2007. Cases were identified as those newly diagnosed with glaucoma (ICD-9 360). For each case, 5 controls were selected and matched to the cases by age and calendar time using density-based sampling. Crude and adjusted rate ratios (RRs) for current and past use of topiramate were computed. As a sensitivity analysis, the risk of glaucoma with a positive control drug (an oral steroid) and a negative control drug (inhaled albuterol) was also assessed. Results: From the initial cohort of 989 591 subjects, 178 264 cases of glaucoma and 891 320 controls were identified. There was a slight increase in the risk of glaucoma among current users of topiramate (RR = 1.23 [95% confidence interval (CI), 1.09-1.40]). This risk was further elevated among new users of the drug (RR = 1.54 [95% CI, 1.09-2.17]). No increase in the risk of glaucoma requiring drug therapy was observed among current topiramate users (RR = 1.09 [95% CI, 0.80-1.61]). Conclusion: We found an increase in the risk of glaucoma with first-time users of topiramate. Future studies are needed to confirm these findings.

Reporting Visual Acuities

2012-05-01

The AJO encourages authors to report the visual acuity in the manuscript using the same nomenclature that was used in gathering the data provided they were recorded in one of the methods listed here. This table of equivalent visual acuities is provided to the readers as an aid to interpret visual acuity findings in familiar units.

Clinical Evaluation of Three Incision Size–Dependent Phacoemulsification Systems

Lixia Luo, Haotian Lin, Mingguang He, Nathan Congdon, Ye Yang, Yizhi Liu — 2012-02-06

Purpose: To compare the outcomes of cataract surgery performed with 3 incision size–dependent phacoemulsification groups (1.8, 2.2, and 3.0 mm). Design: Prospective randomized comparative study. Methods: One hundred twenty eyes of 120 patients with age-related cataract (grades 2 to 4) were categorized according to the Lens Opacities Classification System III. Eligible subjects were randomly assigned to 3 surgical groups using coaxial phacoemulsification through 3 clear corneal incision sizes (1.8, 2.2, and 3.0 mm). Different intraoperative and postoperative outcome measures were obtained, with corneal incision size and surgically induced astigmatism as the main clinical outcomes. Results: There were no statistically significant differences in most of the intraoperative and postoperative outcome measures among the 3 groups. However, the mean cord length of the clear corneal incision was increased in each group after surgery. The mean maximal clear corneal incision thickness in the 1.8-mm group was significantly greater than for the other groups at 1 month. The mean surgically induced astigmatism in the 1.8- and 2.2-mm groups was significantly less than that in the 3.0-mm group after 1 month, without significant difference between the 1.8- and 2.2-mm groups. Conclusions: With appropriate equipment, smaller incisions may result in less astigmatism, but the particular system used will influence incision stress and wound integrity, and may thus limit the reduction in incision size and astigmatism that is achievable.

Relationship Between Corneal Biomechanical Properties, Central Corneal Thickness, and Intraocular Pressure Across the Spectrum of Glaucoma

2012-02-06

Purpose: To evaluate corneal biomechanical properties across the glaucoma spectrum and study the relationship between these measurements and intraocular pressure measured by Goldmann applanation tonometry (GAT-IOP) and central corneal thickness (CCT). Design: Prospective cross-sectional study. Methods: setting: Tertiary-care teaching institute. study population: A total of 323 eyes of 323 participants (71 normal, 101 glaucoma suspect [GS], 38 ocular hypertension [OHT], 59 primary angle-closure disease [PACD], 36 primary open-angle glaucoma [POAG], and 18 normal-tension glaucoma [NTG]) who had received no ophthalmic treatment. observation procedures: Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated IOP (IOPcc), and Goldmann-correlated IOP (IOPg) measured by the Ocular Response Analyzer (ORA). GAT-IOP and CCT recorded in all subjects. main outcome measures: Regression analysis used to determine the relationship between GAT-IOP, CCT, age, CRF, and CH. Bland-Altman plots used to assess agreement between IOP measured by GAT and the ORA (IOPg). Results: CH measurements were significantly less in POAG and NTG compared to normal subjects (P = .034 and P = .030 respectively), regardless of the IOP. The CRF was significantly less in NTG and maximum in POAG and OHT. Regression analysis with CH as dependant variable showed significant association with GAT-IOP and CRF (P < .001) but not CCT, persisting on multivariate analysis (adjusted R2 = 0.483). GAT-IOP correlated strongly with Goldmann-correlated IOP on the ORA (IOPg) (r = 0.82; P < .001), but limits of agreement between the measurements were poor. Conclusions: CH and CRF may constitute a pressure-independent risk factor for glaucoma. CRF appears to influence GAT-IOP measurements more than simple geometric thickness measured by CCT. However, IOP measurements from the ORA are not interchangeable with, and are unlikely to replace, Goldmann applanation tonometry at the present time.

Characteristics of Peripapillary Retinal Nerve Fiber Layer in Preterm Children

Jingyun Wang, Rand Spencer, Joel N. Leffler, Eileen E. Birch — 2012-02-06

Purpose: To examine quantitatively characteristics of the peripapillary retinal nerve fiber layer (RNFL) in preterm children using Fourier-domain optical coherence tomography (FD-OCT). Design: Prospective cross-sectional study. Methods: A 3-mm high-resolution FD-OCT peripapillary RNFL circular scan centered on the optic disc was obtained from right eyes of 25 preterm children (10.6 ± 3.7 years old, 8 preterm and 17 with regressed retinopathy of prematurity with normal-appearing posterior poles) and 54 full-term controls (9.8 ± 3.2 years old). Images were analyzed using Spectralis FD-OCT software to obtain average thickness measurements for 6 sectors (temporal superior, temporal, temporal inferior, nasal inferior, nasal, nasal superior), and the global average. Results: The RNFL global average for preterm children was 8% thinner than for full-term controls. In the preterm group, peripapillary RNFL thickness on the temporal side of the disc was 6% thicker than in full-term controls, while all other peripapillary RNFL sectors were 9% to 13% thinner. In the preterm group, temporal sector peripapillary RNFL thickness was correlated with gestational age (r = −0.47, P < .001), with foveal center total thickness (r = 0.48, P = .008, 1-tailed), and with visual acuity (r = 0.42; P = .026, 1-tailed). Conclusions: The significantly thinner RNFL global average for preterm children suggests that prematurity is associated with subclinical optic nerve hypoplasia. Significant correlations between temporal sector RNFL thickness and both the foveal thickness and visual acuity suggest that the peripapillary RNFL is related to abnormalities in macular development as a result of preterm birth.

Surgical Rehabilitation of the Open Globe Injury Patient

Michael T. Andreoli, Christopher M. Andreoli — 2012-01-20

Purpose: To describe the long-term surgical course of patients with open globe injury. Design: Retrospective case series. Methods: Patients with open globe injuries (848 in total) treated surgically at the Massachusetts Eye and Ear Infirmary between 2000 and 2009 were retrospectively reviewed. Data from presentation, initial repair, and follow-up surgery were analyzed. Results: Among 848 injuries, 1415 surgical procedures were performed. The mean follow-up time was 19.7 months, including 6017 visits. On average, patients required 1.7 surgeries and 7.1 follow-up visits. Factors predicting follow-up surgery included more severe ocular trauma score, worse prerepair visual acuity, retinal hemorrhage, anterior vitrectomy at primary repair, pars plana vitrectomy at primary repair, and lensectomy at primary repair. Patients with zone II injury, hemorrhagic choroidal detachment, and a history of previous ocular surgery tended to require follow-up surgery less frequently. Patients requiring a second surgery tended to have worse visual acuity at presentation and postrepair. Postoperative visual outcomes were worse for patients who underwent vitreoretinal follow-up surgery, likely because of mechanism of injury. Variables associated with inferior visual outcome were worse prerepair visual acuity, postoperative afferent pupillary defect (APD), old age, scleral laceration, and retinal detachment. Conclusion: Open globe injuries require significant surgical follow-up. Patients requiring multiple operations tended to have worse postoperative visual acuity. Patients who underwent vitreoretinal surgery had overall worse visual outcomes. While the first year of surveillance appears to be pivotal in the course of an open globe injury, these patients can expect long-term care from comprehensive and subspecialty ophthalmologists.

Characterization of Diabetic Microaneurysms by Simultaneous Fluorescein Angiography and Spectral-Domain Optical Coherence Tomography

2012-02-02

Purpose: To correlate spectral-domain optical coherence tomography (SD-OCT) findings of perfused diabetic microaneurysms with leakage status on fluorescein angiography (FA) using simultaneous FA and SD-OCT. Design: Retrospective, observational case series. Methods: A total of 173 microaneurysms were analyzed in 50 eyes (14 mild nonproliferative diabetic retinopathy [NPDR]; 22 moderate NPDR; 9 severe NPDR; 5 proliferative diabetic retinopathy) of 40 diabetic patients using simultaneous FA and SD-OCT. The characteristics of microaneurysms were evaluated by 2 masked observers using SD-OCT and correlated with leakage status on FA. Results: External diameter of microaneurysms averaged 104 μm (range 43-266 μm). Some microaneurysm centers (15/173; 9%) and the outermost extent of microaneurysms (113/173; 68%) were localized to the outer half of the retina. Almost all microaneurysms spanned more than 1 retinal layer (157/173; 91%). Most microaneurysms had an internal lumen with homogeneous reflectivity (109/173; 63%) and moderate reflectivity (87/173; 50%). Retinal thickness through microaneurysms as well as the presence of adjacent hyporeflectivity on SD-OCT correlated with increasing leakage status seen on FA (P < .001). Microaneurysm dimensions, percent depth within the retina, retinal layer location, and internal reflectivity by SD-OCT did not correlate significantly with FA leakage status. Conclusions: Simultaneous FA and SD-OCT allows detailed characterization of perfused diabetic microaneurysms. Increased FA leakage of diabetic microaneurysms positively correlated with perianeurysm fluid and retinal thickness. Perfused microaneurysms seen by SD-OCT were localized deeper than the inner nuclear layer.

Retinal Breaks in Small-Gauge Pars Plana Vitrectomy

Rita Ehrlich, Yi Wei Goh, Nadeem Ahmad, Philip Polkinghorne — 2012-02-06

Purpose: To determine the frequency of peripheral iatrogenic retinal breaks in eyes undergoing small-gauge pars plana vitrectomy. Design: Prospective, single-center, noncomparative interventional case series. Methods: A consecutive series of patients that underwent 23- or 25-gauge vitrectomy between July 2010 and the end of October 2010 were included in the study. We excluded patients with retinal detachment, dislocated crystalline lens from complicated cataract surgery, endophthalmitis, and previous history of eye trauma or vitrectomy. We recorded prospectively the frequency of all retinal breaks noted during surgery of patients undergoing 23- or 25-gauge vitrectomy. The indications for vitreoretinal surgery were recorded, as were the location of retinal breaks, the presence or absence of an intact posterior hyaloid, status of lens, method of retinopexy, and use of a tamponade, together with the onset of a rhegmatogenous retinal detachment during the 3-month follow-up interval. Main outcome was rate of entry site breaks in small-gauge vitrectomy. Results: We included 184 patients in this study. The mean age was 65.6 years (SD 13.2) and 46% were male. Retinal breaks occurred in 29 patients (15.7%) but breaks in only 6 (3.2%) were deemed to be related to the sclerotomies. Entry site breaks were not linked to the gauge of the instruments, but retinal breaks were more common in 23-gauge surgeries, although this was not statistically significant. One rhegmatogenous retinal detachment occurred in the postoperative period. Conclusions: Entry site retinal breaks are not common in small-gauge vitrectomy.

Reduced-Fluence Photodynamic Therapy Combined With Intravitreal Bevacizumab for Polypoidal Choroidal Vasculopathy

Min Sagong, Suho Lim, Woohyok Chang — 2012-01-20

Purpose: To evaluate the efficacy and safety of reduced-fluence photodynamic therapy (PDT) combined with bevacizumab for polypoidal choroidal vasculopathy (PCV). Design: Prospective, noncomparative, interventional case series. Methods: Sixteen treatment-naïve patients with polypoidal choroidal vasculopathy were treated with reduced-fluence PDT combined with bevacizumab. All patients were followed up monthly for 12 months with measurements of best-corrected visual acuity (BCVA) and central foveal thickness by optical coherence tomography. Indocyanine green angiography and fluorescein angiography were performed every 3 months. Patients were re-treated with reduced-fluence PDT combined with bevacizumab or with sole injection of bevacizumab when indicated. Results: The mean logMAR BCVA showed significant improvement from 0.76 at baseline to 0.46 at 12 months (P = .002). At 12 months, the BCVA improved in 9 eyes (56.3%) by 3 lines or more, was stable in 6 eyes (37.5%), and decreased in 1 eye (6.3%) because of recurrence of polyps. During the study period, 3 patients (18.8%) had recurrence of polyps and 2 patients (12.5%) had persistent polyps. Mean episodes of reduced-fluence PDT and mean injections of intravitreal bevacizumab over 12 months were 1.44 and 2.44, respectively. Although 3 patients had mild choroidal nonperfusion—1 eye after 1 session of PDT and 2 eyes after 2 sessions—no severe complications, including endophthalmitis, uveitis, or subretinal hemorrhage, developed. Conclusion: Reduced-fluence PDT combined with bevacizumab for PCV seemed to be effective for improving vision and reducing complications. Further study to optimize the light dose of PDT in combination therapy is needed in order to achieve better treatment outcomes for PCV.

Infrared Imaging and Optical Coherence Tomography Reveal Early-Stage Astrocytic Hamartomas Not Detectable by Fundoscopy

2012-02-06

Purpose: To describe and correlate the features of astrocytic hamartomas using multimodal imaging. Design: Prospective, noncomparative, observational case series. Methods: This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared. Results: In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identify 1 occult lesion that was detected with infrared imaging and SD-OCT. SD-OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots. Conclusions: Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors.

Multimodal Fundus Imaging in Choroidal Osteoma

2012-01-23

Purpose: To describe the morphologic features of calcified and decalcified choroidal osteomas using multimodal imaging and correlate these findings with a previous histopathologic study. Design: Retrospective observational case series. Methods: Three patients with choroidal osteoma underwent complete ophthalmologic examination, fundus photography, and multimodal fundus imaging, including Fourier-domain optical coherence tomography (FD-OCT) and blue-light fundus autofluorescence (bAF). Results: FD-OCT imaging of calcified tumors revealed a distinctive latticework pattern of reflectivity resembling the spongy bone structure seen histopathologically. On bAF the fluorescence was relatively well preserved overlying calcified tumors. In decalcified areas 2 patterns of reflectivity were identified: the first consisted of areas of relative hyperreflectivity with a lamellar appearance while the second was characterized by heterogeneous, hyperreflective, mound-like irregular areas associated with some posterior optical shadowing. Decalcified tumor areas had reduced overall fluorescence on bAF. Conclusion: FD-OCT demonstrated different reflectivity patterns in both calcified and decalcified portions of the choroidal osteoma, which may correspond to different stages of tumor evolution. A distinctive latticework pattern of reflectivity similar to spongy bone was seen in calcified tumors. These observations improve our knowledge of the in vivo structure of choroidal osteomas and may have implications for the diagnosis and management of this tumor.

Succinate Increases in the Vitreous Fluid of Patients With Active Proliferative Diabetic Retinopathy

2012-01-20

Purpose: To examine vitreous succinate levels from proliferative diabetic retinopathy (PDR) patients and ascertain their association with PDR activity. Design: Comparative case series. Methods: A total of 81 eyes of 72 PDR patients were divided into active PDR (22 eyes), quiescent PDR (21 eyes), and active PDR with intravitreal bevacizumab injection (38 eyes). Twenty epiretinal membrane (ERM) patients (21 eyes) served as controls. Results: Mean vitreous succinate levels were 1.27 μM in ERM and 2.20 μM in PDR, with the differences statistically significant (P = .03). When comparing mean vitreous succinate levels (active PDR: 3.32 μM; quiescent PDR: 1.02 μM; active PDR with intravitreal bevacizumab injection: 1.20 μM), significant differences were found between active and quiescent PDR (P < .01) and between active PDR and active PDR with intravitreal bevacizumab injection (P < .01). Even though succinate levels were low, retinopathy activities were very high in patients with active PDR with intravitreal bevacizumab injection. Mean vitreous vascular endothelial growth factor (VEGF) levels (active PDR: 1696 pg/mL; quiescent PDR: 110 pg/mL; active PDR with intravitreal bevacizumab injection: n.d.) were similar to previous reports. Mean vitreous erythropoietin levels (active PDR: 703 mIU/mL; quiescent PDR: 305 mIU/mL; active PDR with intravitreal bevacizumab injection: 1562 mIU/mL) suggested very high retinopathy activities in patients with active PDR with intravitreal bevacizumab injection. Conclusions: Succinate, like VEGF, may be an angiogenic factor that is induced by ischemia in PDR. Although succinate is reported to promote VEGF expression, VEGF inhibition decreases succinate. Thus, VEGF, via a positive feedback mechanism, may regulate succinate.

Correlation Between Plasma Pentosidine Concentrations and Retinal Hemodynamics in Patients With Type 2 Diabetes

Eiichi Sato, Taiji Nagaoka, Harumasa Yokota, Atsushi Takahashi, Akitoshi Yoshida — 2012-01-23

Purpose: To investigate whether plasma pentosidine, a well-defined advanced glycation end product, is associated with retinal hemodynamic abnormalities in patients with type 2 diabetes. Design: Prospective cross-sectional study. Methods: Forty-two eyes with type 2 diabetes mellitus were evaluated. The type 2 diabetic eyes were divided into 2 groups: 22 eyes (22 patients; mean age, 61 years) with nondiabetic retinopathy (NDR) and 20 eyes (20 patients; mean age, 61 years) with mild nonproliferative diabetic retinopathy (NPDR). We used a retinal laser Doppler system to measure the arterial diameter, velocity, and blood flow in the major temporal retinal arteries. The pulsatility ratio, a resistive index expressed as the peak systolic to the end diastolic velocity ratio, was calculated from the blood velocity traces. Plasma pentosidine was measured in 42 patients with diabetes using a commercially available competitive enzyme-linked immunosorbent assay. Results: The pulsatility ratio significantly increased in patients with NPDR (4.8 ± 1.5) compared with patients with NDR (3.7 ± 0.8) (P = .0061). No differences in velocity, diameter, or blood flow were seen between the 2 groups. Plasma pentosidine levels also increased significantly (P = .0085) in patients with NPDR (0.057 ± 0.015) compared to patients with NDR (0.047 ± 0.012). The pulsatility ratio was correlated positively with the plasma pentosidine levels in patients with NPDR (Pearson correlation, r = 0.45, P = .044). Multiple regression analysis showed that the plasma pentosidine level was significantly associated with the pulsatility ratio (standardized coefficient, 0.62; P = .009). Conclusions: The vascular rigidity of the retinal arteries may increase with increasing plasma pentosidine in patients with type 2 diabetes with retinopathy.

Peripheral Exudative Hemorrhagic Chorioretinopathy: Polypoidal Choroidal Vasculopathy and Hemodynamic Modifications

Irmela Mantel, Ann Schalenbourg, Leonidas Zografos — 2012-02-06

Purpose: To investigate choroidal vascular abnormalities in peripheral exudative hemorrhagic chorioretinopathy, using dynamic ultrawide-field fluorescein angiography (FA) and indocyanine green angiography (ICGA). Design: Prospective observational case series. Methods: This institutional study comprised a consecutive series of 40 patients (48 eyes) with peripheral exudative hemorrhagic chorioretinopathy. Choroidal vascular abnormalities were assessed with dynamic ultrawide-field (150-degree) FA and ICGA, using the Staurenghi 230 SLO Retina Lens and the Heidelberg scanning laser ophthalmoscope. The main outcome measures were morphologic descriptions of structural vascular abnormalities and choroidal hemodynamics (comparison with 30 normal eyes). Results: The peripheral mass lesions were highly exudative and hemorrhagic, and usually associated with a pigment epithelium detachment. FA revealed nonspecific alterations corresponding to the visible fundoscopic changes (window defects, blockage, staining), but no neovascular membrane. However, despite frequent masking, ICGA showed hyperfluorescent polyp-like structures in the choroid of the lesion area in 33 eyes (69%) and an abnormal choroidal vascular network in 24 eyes (50%). The abnormal choroidal vascular network filled in the arterial or early venous phase, while the polyp-like structures filled some seconds later. Optical coherence tomography revealed the typical dome-shaped elevation of the pigment epithelium over the vascular polyps. Peripheral choriocapillaris closure was observed as well as dilated shunting vessels. Conclusion: Peripheral exudative hemorrhagic chorioretinopathy shares many characteristics (polyp-like choroidal telangiectases, abnormal choroidal vascular networks, exudative and hemorrhagic presentation) with polypoidal choroidal vasculopathy. Clarification of the precise role of these abnormalities requires further studies.

Clinical Features of Newly Diagnosed Cytomegalovirus Retinitis in Northern Thailand

2012-01-20

Purpose: To characterize the clinical manifestations of cytomegalovirus (CMV) retinitis in northern Thailand. Design: Prospective, observational, cross-sectional study. Methods: We recorded characteristics of 52 consecutive patients newly diagnosed with CMV retinitis at a tertiary university-based medical center in northern Thailand. Indirect ophthalmoscopy by experienced ophthalmologists was supplemented with fundus photography to determine the proportion of eyes with various clinical features of CMV retinitis. Results: Of the 52 patients with CMV retinitis, 55.8% were female. All were HIV-positive. The vast majority (90.4%) had started antiretroviral therapy. CMV retinitis was bilateral in 46.2% of patients. Bilateral visual acuity worse than 20/60 was observed in 23.1% of patients. Of 76 eyes with CMV retinitis, 61.8% had zone I disease and 21.6% had lesions involving the fovea. Lesions larger than 25% of the retinal area were observed in 57.5% of affected eyes. CMV retinitis lesions commonly had marked or severe border opacity (47.4% of eyes). Vitreous haze often was present (46.1% of eyes). Visual impairment was more common in eyes with larger retinitis lesions. Retinitis lesion size, used as a proxy for duration of disease, was associated with fulminant appearance (odds ratio, 1.24; 95% confidence interval, 1.01 to 1.51) and marked or severe border opacity (odds ratio, 1.36; 95% confidence interval, 1.11 to 1.67). Based on lesion size, retinitis preceded antiretroviral treatment in each patient. Conclusions: Patients seeking treatment at a tertiary medical center in northern Thailand had advanced CMV retinitis, possibly because of delayed diagnosis. Earlier screening and treatment of CMV retinitis may limit progression of disease and may prevent visual impairment in this population.

Efficacy and Potential Complications of Difluprednate Use for Pediatric Uveitis

Mark A. Slabaugh, Erin Herlihy, Sharel Ongchin, Russell N. van Gelder — 2012-01-20

Purpose: To evaluate the clinical effect of topical difluprednate in pediatric patients for treatment of noninfectious uveitis. Design: Retrospective, observational case series. Methods: Twenty-six eyes of 14 pediatric patients with noninfectious uveitis who were treated with topical difluprednate were evaluated. Anterior and posterior cell grade, visual acuity, intraocular pressure (IOP), and cystoid macular edema (CME) were recorded at each visit. Main outcome measures were changes in anterior segment cell, CME, visual acuity, and IOP and development of a visually significant cataract. Results: A significant (≥ 2-grade decrease or decrease to 0 in anterior segment cell) reduction in anterior segment inflammation was observed during treatment with topical difluprednate in 88% of eyes (22/25) when used as an adjuvant to systemic immunomodulatory therapy. In addition, improvement in CME associated with uveitis was seen in response to topical therapy with difluprednate in 78% of eyes with CME (7/9). A significant IOP response (IOP increase of ≥ 10 mm Hg from baseline and IOP ≥ 24 mm Hg) was seen in 50% of eyes (13/26) and in 50% of patients (7/14); 3 eyes of 2 patients required glaucoma surgery. Cataract formation or progression was observed in 39% of eyes (10/26) and in 43% of patients (6/14); 5 eyes of 3 patients required cataract surgery. Conclusions: Difluprednate is an effective agent for both control of anterior segment inflammation and reduction of CME in pediatric patients with uveitis when used as an adjuvant to systemic immunomodulatory therapy. A high rate of steroid-induced IOP elevation and cataract formation is seen in this population. Close monitoring of pediatric patients receiving difluprednate is recommended.

Pharmacokinetic Study of Vitreous and Serum Concentrations of Triamcinolone Acetonide After Posterior Sub-Tenon's Injection

2012-02-06

Purpose: To compare a theoretical pharmacokinetic model of triamcinolone acetonide after posterior sub-Tenon's injection with experimental serum and undiluted vitreous triamcinolone acetonide concentrations obtained during pars plana vitrectomy. Design: Clinical-practice, prospective, interventional case series study. Methods: This study compared computer-modeled triamcinolone acetonide diffusion after posterior sub-Tenon's injection with triamcinolone acetonide levels in experimental undiluted vitreous and serum samples from 57 patients undergoing vitrectomy assessed via mass spectrometry and high-pressure liquid chromatography. At least 5 pairs of samples were collected at each of 7 time points (1 day, 3 days, and 1, 2, 3, 4, and 8 weeks) after triamcinolone acetonide injection, with 6 controls without injection. Cortisol levels were measured in 31 sets of samples. Results: The theoretical model predicted that triamcinolone acetonide levels in systemic blood, vitreous, and choroidal extracellular matrix would plateau after 3 days at 15 ng/mL, 227 ng/mL and 2230 ng/mL, respectively. Experimental vitreous levels of triamcinolone peaked at 111 ng/mL at day 1, then reached a plateau in the range 15 to 25 ng/mL, while serum triamcinolone levels peaked at day 3 near 35 ng/mL and plateaued near 2 to 8 ng/mL. Serum triamcinolone and cortisol levels were inversely correlated (Spearman −0.42, P = .02). Conclusions: The theoretical model predicts efficient delivery of triamcinolone acetonide from the posterior sub-Tenon's space to the extracellular choroidal matrix. The experimental findings demonstrate low levels of serum triamcinolone that alter systemic cortisol levels and higher vitreous levels lasting at least 1 month. Both assessments support trans-scleral delivery of posterior sub-Tenon's triamcinolone.

AJO History of Ophthalmology Series: Jules Gonin and the Nobel Prize

2012-05-01

The search for an effective treatment for retinal detachment involved many false hypotheses and misconceived surgical techniques, even after De Wecker and Leber in 1875 and 1882 proposed that retinal tears preceded and caused the detachment. When Jules Gonin (1870-1935) insisted that their closure was essential, and therefore, searched carefully for them, he began to have unprecedented success in reattaching the retina from 1916 onwards. In 1930, Gonin's name was presented to the Nobel Prize committee, which then sought the opinion of the prominent Alfred Vogt (1879-1943). Vogt quite wrongly and groundlessly cast doubt on Gonin's priority in discovering this first consistently successful operation for retinal detachment. It was enough for the Nobel committee to defer judgment and eventually pass over Gonin entirely. This has become one of the more glaring omissions in the history of the Nobel Prize.

Graft Rejection Following Descemet Stripping Automated Endothelial Keratoplasty: Features, Risk Factors, and Outcomes

Elaine I. Wu, David C. Ritterband, Guopei Yu, Rebecca A. Shields, John A. Seedor — 2012-01-20

Purpose: To investigate the clinical features, risk factors, and treatment outcomes following immunologic graft rejection in eyes that have undergone Descemet stripping automated endothelial keratoplasty (DSAEK). Design: Retrospective case review. Methods: The charts for 353 DSAEK procedures performed at a single clinical practice at the New York Eye and Ear Infirmary from August 2006 to November 2010 were reviewed. Cases with at least 3 months follow-up were included. Outcome measures included rates of graft rejection, clinical findings, treatment outcomes, and risk factor analysis. Results: Thirty of 353 DSAEKs developed graft rejection (8.5%). Kaplan-Meier rate of rejection was 6.0% at 1 year (n = 175), 14.0% at 2 years (n = 79), and 22.0% at 3 years (n = 39). Rejection episodes occurred between 0.8 and 34 months. Clinical findings included anterior chamber cells, keratic precipitates, endothelial rejection line, and host-donor interface vascularization. Risk factors for development of graft rejection were cessation of postoperative steroid (hazard ratio 5.49, P < .0001) and black race (hazard ratio 2.71, P = .02). Recipient age, sex, surgical indication, glaucoma, postoperative steroid response, corneal neovascularization or peripheral anterior synechiae, graft size, prior keratoplasty in fellow eye, and concurrent or subsequent procedures were not associated with graft rejection. Twenty-two out of 30 rejection episodes (73.3%) resolved with steroid treatment. Conclusions: Graft rejection is an important complication following DSAEK. In contrast to penetrating keratoplasty, rejection following DSAEK is almost exclusively endothelial. Among risk factors traditionally associated with graft rejection, cessation of topical steroids was most significant. Prompt recognition and treatment of DSAEK rejection can lead to favorable outcomes.

Causes of Glaucoma After Descemet Membrane Endothelial Keratoplasty

2012-01-27

Purpose: To describe the incidence and causes of glaucoma after Descemet membrane endothelial keratoplasty (DMEK). Design: Nonrandomized prospective cohort study at a tertiary referral center. Methods: The incidence of glaucoma was evaluated in the first 275 consecutive eyes that underwent DMEK for Fuchs endothelial dystrophy (260 eyes) or bullous keratopathy (15 eyes). Glaucoma was defined as a postoperative intraocular pressure (IOP) elevation of ≥24 mm Hg, or ≥10 mm Hg from the preoperative baseline. If possible, the cause of glaucoma was identified, and best-corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative course were documented, with a mean follow-up of 22 (± 13) months. Results: Overall, 18 eyes (6.5%) showed postoperative glaucoma after DMEK. Seven eyes (2.5%) had an exacerbation of a pre-existing glaucoma. Eleven eyes (4%) presented with a de novo IOP elevation, associated with air bubble–induced mechanical angle closure (2%), steroid response (0.7%), or peripheral anterior synechiae (0.4%), or without detectable cause (0.7%). Two eyes (0.7%) required glaucoma surgery after DMEK. At 6 months, all eyes had a BCVA of ≥20/40 (≥0.5), and 81% reached ≥20/25 (≥0.8) (n = 16); mean ECD was 1660 (± 554) cells/mm2 (n = 15) (P > .1). Conclusion: Glaucoma after DMEK may be a relatively frequent complication that could be avoided by reducing the residual postoperative air bubble to 30% in phakic eyes, applying a population-specific steroid regime, and avoiding decentration of the Descemet graft. Eyes with a history of glaucoma may need close IOP monitoring in the first postoperative months, especially in eyes with an angle-supported phakic intraocular lens.

Surgical and Visual Outcomes of the Type I Boston Keratoprosthesis for the Management of Aniridic Fibrosis Syndrome in Congenital Aniridia

2012-01-23

Purpose: To report the clinical features and surgical management of aniridic fibrosis syndrome using the type I Boston Keratoprosthesis (KPro). Design: Interventional case series. Methods: Retrospective chart review of 9 eyes in 9 patients with congenital aniridia that developed aniridic fibrosis syndrome. Results: All patients had clinical diagnosis of congenital aniridia. Previously, all patients had undergone cataract surgery with posterior chamber intraocular lens (IOL) implantation and 7 patients had existing tube shunts. In all cases, fibrosis presented as progressive retrocorneal and retrolenticular membrane formation causing displacement of the IOL and secondary corneal decompensation. Two eyes had tractional folds in the retina with posterior extension of the membrane. The management included IOL explantation in 7 of 9 cases, removal of fibrosis with pars plana vitrectomy in all 9 patients, and implantation of a type I Boston KPro in all eyes. At a mean final follow-up of 26.1 months (range 6 to 48 months), vision remained improved in all patients. No patient had recurrence of the fibrotic membrane after KPro implantation. Conclusion: This study represents another case series describing aniridic fibrosis syndrome and the largest study to report utilization of the type I Boston KPro in such patients. As the fibrosis can cause IOL dislocation, corneal decompensation, hypotony, and retinal detachment, monitoring for aniridic fibrosis syndrome in congenital aniridia with early surgical intervention is recommended. Type I Boston KPro may be considered in the surgical treatment of this condition.

The Effect of Corneal Wavefront Aberrations on Corneal Pseudoaccommodation

Elizabeth Yeu, Li Wang, Douglas D. Koch — 2012-02-07

Purpose: To determine the effect on corneal pseudoaccommodation of anterior corneal wavefront aberrations in normal corneas and corneas with prior myopic or hyperopic photorefractive keratectomy (PRK) or laser-assisted in situ keratomileusis (LASIK). Design: Theoretical study. Methods: In 220 normal eyes, 102 myopic-PRK eyes, and 106 hyperopic-LASIK/PRK eyes, anterior corneal higher-order aberrations (HOAs, third to sixth order, 6- and 4-mm pupils) were computed from the Atlas corneal elevation data using the VOL-CT program. Using the ZernikeTool, corneal optical image quality was evaluated by the polychromatic modulation transfer function with Stiles-Crawford effect. Defocus from −3.0 diopters (D) to +3.0 D was added to corneal HOAs, and depth of focus was defined as the ranges over which the polychromatic modulation transfer function maintains 80% of the peak value (DOF80) and 50% of the peak value (DOF50). The depth of focus values between groups were compared, stepwise multiple regression was used to assess if any Zernike terms significantly contributed to the depth of focus, and correlation analysis was performed to evaluate the correlation between depth of focus and corneal HOAs. Results: The depth of focus varied widely between corneas, especially in corneas with prior hyperopic-LASIK/PRK. For 6-mm pupil, mean depth of focus values in myopic-PRK and hyperopic-LASIK/PRK corneas were significantly greater than those for normal corneas, and for 4-mm pupil, depth of focus values in hyperopic-LASIK/PRK corneas were greater than those in normal and myopic-PRK corneas. Zernike terms significantly contributing to both DOF80 and DOF50 were fourth- and sixth-order spherical aberration and fourth- and sixth-order astigmatism in normal corneas, third-order vertical coma and fourth-order tetrafoil in myopic-PRK corneas, and third-order vertical coma and fourth-order astigmatism in hyperopic-LASIK/PRK corneas. Depth of focus had weak to moderate positive correlation with HOAs (Pearson correlation coefficient r ranged from 0.300 to 0.583). Conclusion: These theoretical calculations suggest that certain corneal wavefront aberrations affect corneal pseudoaccommodation. To predict corneal pseudoaccommodation, the most important Zernike term is spherical aberration in normal eyes and coma in eyes with prior laser corneal surgery.

Sequential Topical Riboflavin With or Without Ultraviolet A Radiation With Delayed Intracorneal Ring Segment Insertion for Keratoconus

2012-01-20

Purpose: To report refractive, topographic, pachymetric, tonometric, and corneal biomechanical outcomes 24 months after corneal cross-linking (CXL), followed by insertion of intrastromal corneal ring segments (ICRS) in keratoconic eyes. Design: Prospective randomized clinical trial. Methods: settings: Institutional. study population: Thirty-nine eyes of 31 patients, allocated into 2 groups. intervention: Patients in the CXL group underwent corneal CXL with riboflavin and ultraviolet A (UVA) light. Patients in the riboflavin eyedrops group received riboflavin 0.1% (w/v) eyedrops – 20% dextran solution for 1 month. After 3 months, all patients underwent insertion of ICRS. main outcome measures: Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and topography were evaluated at baseline, at 1 month and 3 months after CXL or riboflavin eyedrops, and again at 1-, 3-, 6-, 12-, and 24-month intervals after ICRS insertion. Results: Mean (standard deviation [SD]) baseline UCVA and BSCVA in the CXL group and the riboflavin eyedrops group were 1.12 (0.59) and 0.84 (0.49), and 0.68 (0.43) and 0.45 (0.23), respectively; 24-month mean (SD) UCVA and BSCVA in the CXL group and the riboflavin eyedrops group were 0.79 (0.50) and 0.62 (0.28), and 0.52 (0.45) and 0.32 (0.21), respectively, with no statistically significant difference between groups (P = .70 and P = .78).There were no statistical differences between groups postoperatively at 24 months for all 3 topographic parameters, flattest-K1 (P = .81), steepest-K2 (P = .68), and average keratometry (mean power; P = .52). Conclusions: ICRS insertion, with or without prior CXL, showed no difference between groups in terms of refractive, topographic, pachymetric, tonometric, and corneal biomechanical results at 24 months.

Reading Performance After Implantation of a Modified Corneal Inlay Design for the Surgical Correction of Presbyopia: 1-Year Follow-up

2011-11-21

Purpose: To evaluate change in different reading performance parameters after monocular ACI7000PDT corneal inlay implantation for the improvement of near and intermediate vision. Design: Prospective, interventional case series. Methods: Twenty-four patients were scheduled for corneal inlay implantation in the nondominant eye in a university outpatient surgery center. Naturally emmetropic and presbyopic patients between 45 and 60 years of age, with uncorrected distance visual acuity of at least 20/20 in both eyes, without any additional ocular pathology were eligible for inclusion. Bilateral uncorrected reading acuity, mean and maximum reading speed, and smallest log-scaled print size were evaluated with the standardized Radner Reading Charts. Measurements of reading parameters and reading distance were performed with the Salzburg Reading Desk (SRD). Minimum postoperative follow-up was 12 months. Results: The reading desk results showed significant changes in each parameter tested. After 12 months the mean reading distance changed from the preoperative value of 46.7 cm (95% CI: 44.1–49.3) to 42.8 cm (95% CI: 40.3–45.3, P < .004), and the mean reading acuity “at best distance” improved from 0.33 logRAD (95% CI: 0.27–0.39) to 0.24 logRAD (95% CI: 0.20–0.28, P < .005). Mean reading speed increased from 141 words per minute (wpm, 95% CI: 133–150) to 156 wpm (95% CI: 145–167, P < .003), maximum reading speed increased from 171 wpm (95% CI: 159–183) to 196 wpm (95% CI: 180–212, P = .001), and the smallest print size improved from 1.50 mm (95% CI: 1.32–1.67) to 1.12 mm (95% CI: 1.03–1.22, P < .001). Conclusions: After ACI7000PDT implantation, there were significant changes in all tested reading performance parameters in emmetropic presbyopic patients. These 1-year results indicate that the inlay seems to be an effective treatment for presbyopia.

Corneal Collagen Cross-linking With Riboflavin and Ultraviolet-A Irradiation in Patients With Thin Corneas

Zhen-Yong Zhang, Xing-Ru Zhang — 2012-05-01

We read with interest the paper entitled “Corneal collagen cross-linking with riboflavin and ultraviolet-A irradiation in patients with thin corneas,” and would like to offer comments and raise our concerns when considering collagen cross-linking (CXL) procedure for patients with a thin cornea.

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George D. Kymionis — 2012-05-01

We would like to respond to the comments by Zhang and associate regarding our article entitled “Corneal collagen cross-linking with riboflavin and ultraviolet-A irradiation in patients with thin corneas,” published in the Journal.

Ocular Surface Disease and Quality of Life in Patients With Glaucoma

Halit Oguz — 2012-05-01

I read with interest the valuable cross-sectional study performed by Skalicky and associates in the January 2012 issue of the Journal. The authors investigated the relationship between ocular surface disease and glaucoma-related quality of life, glaucoma severity, and treatment in patients with open-angle glaucoma. They found that ocular surface disease index (OSDI) scores and the number of patients with ocular surface disease (OSD) increased with increasing glaucoma severity. In addition, OSDI was significantly correlated with Glaucoma Quality of Life-15 summary score, glaucoma severity, multiple topical glaucoma medications, worse eye mean deviation and pattern standard deviation, use of topical beta blockers, topical carbonic anhydrase inhibitors, daily dose of benzalkonium chloride, and glaucoma filtration surgery. In addition to preservatives in glaucoma medications, they mentioned in the article that elevated and exposed blebs can aggravate OSD symptoms. I think this merits more discussion and explanation: McDonald and Brubaker previously suggested tear meniscus and meniscus-induced thinning, and ocular surface irregularities had ectopic meniscus and a thinned meniscus area and resultant staining. They reported that tear film fractured in these thin areas. Also, they predicted that perilimbal elevations such as filtering blebs have secondary tear menisci and adjacent thinning area. I think the ectopic meniscus and thinning area can be demonstrated by video-meniscometer.

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Simon E. Skalicky, Ivan Goldberg, Peter McCluskey — 2012-05-01

We thank Professor Oguz for commenting on our paper. While dysesthetic blebs following glaucoma drainage surgery contribute to symptomatic ocular surface disease (OSD), there is little data regarding the specific etiology. It is likely to be multifactorial. Budenz and associates, investigating 97 patients with unilateral trabeculectomy blebs, found that young age, bleb exposure in the interpalpebral fissure, height of the bleb adjacent to the cornea, and bubbles in the tear film on blinking were predictive of dysesthesia. Only 2 patients had adjacent dellen and 6 an epithelial defect; hence, no significant results were obtained regarding these proposed mechanisms. Surprisingly, the type of antifibrotic agent used (none, 5-fluorouracil, or mitomycin C) was not predictive of dysesthesia, as these agents may lead to limbal stem cell damage.

Combined Intravitreal Ranibizumab and Photodynamic Therapy for Retinal Angiomatous Proliferation

Mee Yon Lee, Kyu Seop Kim, Won Ki Lee — 2012-05-01

The recent article by Saito and associates was of great interest to us. These investigators conducted a retrospective analysis of patients with retinal angiomatous proliferation (RAP) following combination use of 3 monthly consecutive ranibizumab intravitreal injections and photodynamic therapy (PDT). This strategy apparently proved effective at 1 year in terms of morphologic and functional outcomes. In a prior prospective study, we too achieved promising results with this regimen (3 monthly ranibizumab plus PDT) in the treatment of advanced RAP with serous pigment epithelial detachment (PED). While Saito and associates performed PDT with fluorescein angiographic (FA) guidance 1 or 2 days after the first injection, we opted for indocyanine green angiography (ICGA)-guided PDT 7 days from initial injection.

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Masaaki Saito, Tomohiro Iida, Mariko Kano — 2012-05-01

We thank Lee and associates for their interest and comments regarding our paper, “Combined intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation.” We had an interest in reading the article reported by Lee and associates. Freund and associates described “PPP,” referred to as pharmacology–pause–photodynamic therapy (PDT), in cases with combination therapy of intravitreal triamcinolone acetonide and PDT for retinal angiomatous proliferation (RAP) patients. The method of PPP was well conceived based on the hypothesis that verteporfin may leak into the retinal cystic spaces, and to avoid predisposing the retinal layers to photochemical damage.

Intralesional Triamcinolone Acetonide Injection Versus Incision and Curettage for Primary Chalazia: A Prospective, Randomized Study

Jonathan H. Norris — 2012-05-01

I read with interest the article by Ben Simon and associates comparing the use of intralesional triamcinolone acetonide (TA) with standard incision and curettage (I&C) treatment. The authors presented a single-center, prospective, randomized controlled clinical trial. The results of this study provide some evidence that TA may be useful in patients with primary chalazia and, despite limited follow-up, there were no reported adverse events. When considering a paradigm shift in practice from the standard I&C treatment and using this trial as evidence for such a change, I believe there are some key issues that need addressing.

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Guy J. Ben Simon — 2012-05-01

We thank Dr Norris for his useful comments regarding our article. Patients were randomized according to which day they presented to the clinic. The office manager assigns each new patient to the first available clinic day until reaching a predetermined quota. This quota varies regarding how many physicians attend the oculoplastic clinic that day; hence, we do believe it is a good method of randomization even if not perfect. Moreover, only patients seen by the corresponding author (G.B.S.) were enrolled into the study, and this is solely by chance; if another physician examined them he would treat them according to his belief.

Keratocyte Density 3 Months, 15 Months, and 3 Years After Corneal Surface Ablation With Mitomycin C

Carrie Huisingh, Gerald McGwin — 2012-05-01

The recently published study by Benito-Llopis and associates is described as a case series; however, this is incorrect. A case series study would involve following a group of patients who have a similar diagnosis or are undergoing the same procedure over a certain period without the use of controls. In the current study, the author selected 2 groups of participants based on an exposure, or risk factor, of interest: 1 with eyes that underwent laser-assisted subepithelial keratocyte (LASEK) and the other with nonoperated eyes. As such, this study design is better described as a cohort study. Unfortunately, this is not merely a semantic issue as it has implications for the appropriate statistical analysis and, therefore, the proper interpretation of the observed results. None of the analyses the authors mention use paired statistics, which are needed to account for the clustering effect when comparing the same unit of observation (in this case, eyes) between different time points. Additionally, the authors report using the Bonferroni test to test the normality of the data, concluding that the data are normally distributed. However, we are unaware of any Bonferroni test used to measure normality, and given the nature of the data, it is unlikely that the data are normally distributed. If they wrongly concluded that the data are normally distributed, then the use of parametric statistical tests is also incorrect. The authors are strongly urged to conduct a reanalysis of their study data and provide readers with the appropriate measures of association and P values, amending their interpretation as warranted.

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2012-05-01

We would like to thank Carrie Huisingh and Gerald McGwin for their interest in our paper. We have to state that we strongly disagree with most of their comments. First, they suggest that “cohort study” defines our study better than “case series.” This is not correct. A “cohort study” is defined as “the study of a population exposed to a risk factor which may influence the occurrence of a given disease or another outcome.” This is clearly not the case of our study, which analyzes the effect of LASEK surgery on the keratocyte population. There is not a disease or a given outcome to reach, so we believe that “case series” is, by far, a more appropriate description.

Prophylactic Selective Laser Trabeculoplasty in the Prevention of Intraocular Pressure Elevation After Intravitreal Triamcinolone Acetonide Injection

Zeynep Aktas, Gokcen Deniz, Murat Hasanreisoglu — 2012-05-01

In the article titled “Prophylactic Selective Laser Trabeculoplasty in the Prevention of Intraocular Pressure Elevation After Intravitreal Triamcinolone Acetonide Injection,” by Bozkurt and associates, the authors mentioned that the intraocular pressure (IOP) elevation after intravitreal triamcinolone acetonide injection may be prevented by performing selective laser trabeculoplasty (SLT) before the injection, especially in cases with a baseline IOP of 21 mm Hg or more. This study provides a valuable contribution to the literature since glaucoma has been one of the most common problems after intravitreal triamcinolone injection. Furthermore, baseline IOP was reported to be a risk factor for increased IOP after the intravitreal triamcinolone injection. Applying SLT to these patients before the procedure might be practical and easy way to solve this problem to some extent.

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Necip Kara, Ercument Bozkurt — 2012-05-01

We appreciate the interest and comments of Aktas and associates concerning our article. They reviewed our study and reported their concerns about the absence of further examination of participants such as retinal fiber layer thickness (RNFL) measurements and visual field (VF) tests for detection of glaucoma. We agree that the study has some limitations in this respect. Although clinical examination of the optic nerve head and retinal nerve fiber layer is essential for the detection of glaucoma, currently available devices such as optical coherence tomography (OCT) and scanning laser polarimetry (SLP) would facilitate the diagnosis and monitoring of glaucomatous optic neuropathy. Several previous studies reported that diabetic patients without glaucoma have a thinner RNFL than nondiabetic healthy subjects, based on measurements with clinically available devices. Although effects of diabetes on RNFL have been reported, no significant difference was found in the cup-to-disc ratio between diabetic and normal eyes. Also, studies performed with OCT and SLP have documented that peripapillary RNFL thinning is increased with disease severity. RNFL loss in eyes of patients with diabetes mellitus is a common finding, but is not associated with an enlarged cup, and thus can be differentiated from glaucoma-related RNFL defects, which accompany glaucomatous excavation of the disc. In our study RNFL thickness was not used because of the effect of diabetes on RNFL thickness at baseline, to avoid a bias. We did compare the RNFL thickness between the baseline and postinjection period only in patients with increased intraocular pressure following intravitreal triamcinolone injection. Visual field testing is one of the primary methods used for detection of glaucomatous functional abnormalities. Reliability of visual field testing is essential for accurate diagnosis and follow-up of glaucoma. In our study, many patients with diabetic macular edema and low visual acuity had unreliable test results because of excessive fixation losses and false-positive errors in conventional (white-on-white) visual field test. Hence, VF tests were not considered at the baseline. After reduction of macular edema following intravitreal triamcinolone injection, however, we assessed VF test results only for patients who had had increased intraocular pressure following intravitreal triamcinolone injection and who had reliable test results. To avoid a bias, we did not compare RNFL thickness and VF test results between groups at baseline.

Aqueous Humor Levels of Vascular Endothelial Growth Factor Before and After Intravitreal Bevacizumab in Type 3 Versus Type 1 and 2 Neovascularization: A Prospective, Case-Control Study

Carrie Huisingh, Gerald McGwin — 2012-05-01

The recently published study by Dell'omo and associates is described as a prospective case-control study; however, this is incorrect. The study participants were selected based on previously untreated type 1, 2, and 3 wet age-related macular degeneration (AMD) and were matched with respect to age. The participants were followed up prospectively to compare the levels of vascular endothelial growth factor. Although AMD is a disease state, the authors' underlying hypothesis is that AMD affects vascular endothelial growth factor, and in this context of their study, AMD is viewed as a risk factor. As such, their study describes a prospective, age-matched cohort study, not a case-control study. This error has implications for the appropriate statistical analysis, and therefore, the proper interpretation of the observed results. A number of statistical tests are described in the Methods; it is not clear whether those tests that are described have been applied appropriately. For example, it is not clear if the correlations in Table 2 reflect data from a single point in time or over time. If over time, then the Spearman correlations would not be appropriate, because it does not account for clustering. Therefore, Table 2 is either poorly constructed or incorrect. At a minimum, the authors should specify at what time points the correlations were drawn. The authors are strongly urged to conduct a reanalysis of their study data and provide readers with the appropriate measures of association and P values, amending their interpretation as warranted.

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Roberto Dell'Omo, Ciro Costagliola — 2012-05-01

We thank Drs Huising and McGwin for commenting on our article. Although we acknowledge that defining the study as a prospective, case-control one may appear incorrect and apparently misleading, we contend that the 2 terms actually refer to 2 different phases of data analysis in the course of the study.

Antibiotic Use and Antimicrobial Resistance

Stephen Jae Kim — 2012-05-01

I read with great interest the article by Alabiad and associates entitled, “Antimicrobial Resistance Profiles of Ocular and Nasal Flora in Patients Undergoing Intravitreal Injections.” I would like to commend the authors for trying to address an important issue. I have some comments about their study design that may explain their conflicting results with the Antibiotic Resistance of Conjunctiva and Nasopharynx Evaluation (ARCANE) Study.

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Chrisfouad R. Alabiad, Darlene Miller, Joyce C. Schiffman, Janet L. Davis — 2012-05-01

We thank Dr Kim for his insight into our article. Our study is not as well designed as the ARCANE study, because we did not follow up sensitivity to antibiotics over time within a patient. However, measures were taken to minimize the confounders mentioned by Dr Kim. A clear standard of care had been established previously at our institution for intravitreal injections. A single application of a topical fluoroquinolone was instilled in the eye after each injection, and each patient was supplied with a new sample of topical fluoroquinolone at each visit, with written instructions that were verbalized by the patient before discharge from the clinic. Almost all previous injections (more than 95%) had been performed at our institution. It is also true that eyes in our study received intravitreal injections over different intervals; however, most were within 1 to 2 months of each other. This also was true in the ARCANE study, in which eyes received as few as 5 or as many as 13 injections within 1 year.

2012-05-01

American Journal of Ophthalmology

Glaucoma Filtration Surgery: Trabeculectomy or Tube Shunt?

Treatment Outcomes in the Tube Versus Trabeculectomy (TVT) Study After Five Years of Follow-up

Postoperative Complications in the Tube Versus Trabeculectomy (TVT) Study During Five Years of Follow-up

Diagnostic Capability of Spectral-Domain Optical Coherence Tomography for Glaucoma

Use of Topiramate and Risk of Glaucoma: A Case-Control Study

Reporting Visual Acuities

Clinical Evaluation of Three Incision Size–Dependent Phacoemulsification Systems

Relationship Between Corneal Biomechanical Properties, Central Corneal Thickness, and Intraocular Pressure Across the Spectrum of Glaucoma

Characteristics of Peripapillary Retinal Nerve Fiber Layer in Preterm Children

Surgical Rehabilitation of the Open Globe Injury Patient

Characterization of Diabetic Microaneurysms by Simultaneous Fluorescein Angiography and Spectral-Domain Optical Coherence Tomography

Retinal Breaks in Small-Gauge Pars Plana Vitrectomy

Reduced-Fluence Photodynamic Therapy Combined With Intravitreal Bevacizumab for Polypoidal Choroidal Vasculopathy

Infrared Imaging and Optical Coherence Tomography Reveal Early-Stage Astrocytic Hamartomas Not Detectable by Fundoscopy

Multimodal Fundus Imaging in Choroidal Osteoma

Succinate Increases in the Vitreous Fluid of Patients With Active Proliferative Diabetic Retinopathy

Correlation Between Plasma Pentosidine Concentrations and Retinal Hemodynamics in Patients With Type 2 Diabetes

Peripheral Exudative Hemorrhagic Chorioretinopathy: Polypoidal Choroidal Vasculopathy and Hemodynamic Modifications

Clinical Features of Newly Diagnosed Cytomegalovirus Retinitis in Northern Thailand

Efficacy and Potential Complications of Difluprednate Use for Pediatric Uveitis

Pharmacokinetic Study of Vitreous and Serum Concentrations of Triamcinolone Acetonide After Posterior Sub-Tenon's Injection

AJO History of Ophthalmology Series: Jules Gonin and the Nobel Prize

Graft Rejection Following Descemet Stripping Automated Endothelial Keratoplasty: Features, Risk Factors, and Outcomes

Causes of Glaucoma After Descemet Membrane Endothelial Keratoplasty

Surgical and Visual Outcomes of the Type I Boston Keratoprosthesis for the Management of Aniridic Fibrosis Syndrome in Congenital Aniridia

The Effect of Corneal Wavefront Aberrations on Corneal Pseudoaccommodation

Sequential Topical Riboflavin With or Without Ultraviolet A Radiation With Delayed Intracorneal Ring Segment Insertion for Keratoconus

Reading Performance After Implantation of a Modified Corneal Inlay Design for the Surgical Correction of Presbyopia: 1-Year Follow-up

Corneal Collagen Cross-linking With Riboflavin and Ultraviolet-A Irradiation in Patients With Thin Corneas

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Ocular Surface Disease and Quality of Life in Patients With Glaucoma

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Combined Intravitreal Ranibizumab and Photodynamic Therapy for Retinal Angiomatous Proliferation

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Intralesional Triamcinolone Acetonide Injection Versus Incision and Curettage for Primary Chalazia: A Prospective, Randomized Study

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Keratocyte Density 3 Months, 15 Months, and 3 Years After Corneal Surface Ablation With Mitomycin C

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Prophylactic Selective Laser Trabeculoplasty in the Prevention of Intraocular Pressure Elevation After Intravitreal Triamcinolone Acetonide Injection

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Aqueous Humor Levels of Vascular Endothelial Growth Factor Before and After Intravitreal Bevacizumab in Type 3 Versus Type 1 and 2 Neovascularization: A Prospective, Case-Control Study

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Antibiotic Use and Antimicrobial Resistance

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Contents