Journals RSS : Gourt

The Cost-effectiveness of Welcome to Medicare Visual Acuity Screening and a Possible Alternative Welcome to Medicare Eye Evaluation Among Persons Without Diagnosed Diabetes Mellitus [Clinical Sciences]

Objective To estimate the cost-effectiveness of visual acuity screening performed in primary care settings and of dilated eye evaluations performed by an eye care professional among new Medicare enrollees with no diagnosed eye disorders. Medicare currently reimburses visual acuity screening for new enrollees during their initial preventive primary care health check, but dilated eye evaluations may be a more cost-effective policy. Design Monte Carlo cost-effectiveness simulation model with a total of 50 000 simulated patients with demographic characteristics matched to persons 65 years of age in the US population. Results Compared with no screening policy, dilated eye evaluations increased quality-adjusted life-years (QALYs) by 0.008 (95% credible interval [CrI], 0.005-0.011) and increased costs by $94 (95% CrI, –$35 to $222). A visual acuity screening increased QALYs in less than 95% of the simulations (0.001 [95% CrI, –0.002 to 0.004) and increased total costs by $32 (95% CrI, –$97 to $159) per person. The incremental cost-effectiveness ratio of a visual acuity screening and an eye examination compared with no screening were $29 000 and $12 000 per QALY gained, respectively. At a willingness-to-pay value of $15 000 or more per QALY gained, a dilated eye evaluation was the policy option most likely to be cost-effective. Conclusions The currently recommended visual acuity screening showed limited efficacy and cost-effectiveness compared with no screening. In contrast, a new policy of reimbursement for Welcome to Medicare dilated eye evaluations was highly cost-effective.

Lack of Thrombospondin 1 and Exacerbation of Choroidal Neovascularization [Laboratory Sciences]

Objectives To assess the impact of thrombospondin 1 (TSP1) deficiency on choroidal neovascularization (CNV) and to determine whether administration of a TSP1 antiangiogenic mimetic peptide attenuates CNV. Methods The impact of TSP1 deficiency on laser-induced CNV was assessed using wild-type (TSP1+/+) and TSP1-deficient (TSP1–/–) mice. Three laser burns were placed in each eye of TSP1+/+ and TSP1–/– mice to induce CNV. Intravitreal injection of the TSP1 mimetic peptide was performed on days 1 and 7 postlaser in the mice. For quantitative measurements of neovascularization, intercellular adhesion molecule 2 staining was performed at 14 days postlaser of the choroidal-sclera flat mounts. The recruitment of macrophages to the sites of damage was investigated by immunohistochemistry. The CNV area was measured by intercellular adhesion molecule 2 staining and use of ImageJ software. Results The TSP1–/– mice exhibited significantly larger areas of neovascularization on choroidal flat mounts compared with TSP1+/+ mice. This was consistent with enhanced recruitment of macrophages in TSP1–/– mice compared with TSP1+/+ mice 3 days postlaser. The development of CNV was significantly attenuated in mice receiving the TSP1 antiangiogenic mimetic peptide compared with those receiving vehicle alone. Conclusions Deficiency of TSP1 contributes to enhanced choroidal neovascularization. This is consistent with the anti-inflammatory and antiangiogenic activity of TSP1. The TSP1 antiangiogenic peptide was effective in attenuation of CNV. Clinical Relevance Intravitreal injection of TSP1 antiangiogenic mimetic peptides may provide alternative treatment for CNV.

Spectral-Domain Optical Coherence Tomographic Assessment of Severity of Cystoid Macular Edema in Retinopathy of Prematurity [Clinical Sciences]

Objective To investigate whether the severity of cystoid macular edema (CME) in neonates who were 31 to 36 weeks' postmenstrual age, as viewed by spectral-domain optical coherence tomography (SD-OCT) imaging, predicts the severity of retinopathy of prematurity (ROP) or is related to systemic health. Design Of 62 prematurely born neonates in a prospective institutional review board–approved study, 42 met the following inclusion criteria: at least 1 SD-OCT imaging session prior to 37 weeks' postmenstrual age and prior to ROP laser treatment, if a laser treatment was performed, and an ophthalmic ROP examination at or after 41 weeks' postmenstrual age, evidence of complete retinal vascularization in zone III, or documentation through telephone report of such information after transfer of care. Measures of CME severity, including central foveal thickness, retinal layer thicknesses, and foveal-to-parafoveal thickness ratio in 1 eye per subject, were compared with ROP outcomes: laser treatment, maximum plus disease, and maximum ROP stage. Systemic health factors were also correlated. Results Cystoid macular edema was present in 50% of neonates. Multiple elongated cystoid structures within the inner nuclear layer were most common. The presence of CME was not associated with ROP outcomes. The central foveal thickness, the thickness of the inner retinal layers, and the foveal-to-parafoveal thickness ratio were higher in eyes that required laser treatment or that developed plus disease or ROP stage 3. Cystoid macular edema was not clearly associated with systemic factors. Conclusions Cystoid macular edema is common in premature infants screened for ROP before 37 weeks' postmenstrual age, with the most common SD-OCT phenotype of a bulging fovea from multiple elongated cystoid spaces. Detection of CME is not associated with ROP severity; however, tomographic thickness measurements could potentially predict a higher risk of requiring laser treatment or developing plus disease or ROP stage 3. Systemic health factors are probably not related to the development of CME.

In Vivo Evaluation of Focal Lamina Cribrosa Defects in Glaucoma [Clinical Sciences]

Objectives To assess focal lamina cribrosa (LC) defects in glaucoma using enhanced depth imaging optical coherence tomography and to investigate their spatial relationships with neuroretinal rim and visual field loss. Methods Serial horizontal and vertical enhanced depth imaging optical coherence tomographic images of the optic nerve head were obtained from healthy subjects and those with glaucoma. Focal LC defects defined as anterior laminar surface irregularity (diameter, >100 µm; depth, >30 µm) that violates the normal smooth curvilinear contour were investigated regarding their configurations and locations. Spatial consistency was evaluated among focal LC defects, neuroretinal rim thinning/notching, and visual field defects. Results Forty-six healthy subjects (92 eyes) and 31 subjects with glaucoma (45 eyes) were included. Ninety-eight focal LC defects representing various patterns and severity of laminar tissue loss were found in 34 eyes with glaucoma vs none in the healthy eyes. Seven of 11 eyes with glaucoma with no visible focal LC defect had a deeply excavated optic disc with poor LC visibility. Eleven focal LC defects presented clinically as an acquired pit of the optic nerve, and the others as neuroretinal rim thinning/notching. Focal LC defects preferably occurred in the inferior/inferotemporal far periphery of the LC including its insertion. Eyes with focal LC defects limited to the inferior half of the optic disc had greater sensitivity loss in the superior visual hemifield and vice versa. Conclusions Mechanisms of LC deformation in glaucoma include focal loss of laminar beams, which may cause an acquired pit of the optic nerve in extreme cases. Focal LC defects occur in tandem with neuroretinal rim and visual field loss.

A Prospective Pilot Study of Treatment Outcomes for Amblyopia Associated With Myopic Anisometropia [Clinical Sciences]

Objectives To determine the efficacy of refractive correction alone and patching treatment with near activities on amblyopia associated with myopic anisometropia in children aged 4 to less than 14 years. The associations of visual acuity (VA) improvement with age, degree of anisometropia, patching compliance, presence of strabismus, and presence of eccentric fixation were also investigated. Methods Seventeen amblyopic children were recruited (range of VA in the amblyopic eye, 20/80 to 20/400). Visual acuity was assessed at 4, 8, 12, and 16 weeks while participants wore spectacles and/or contact lenses for full refractive correction. Patching treatment was initiated at the 16-week visit. The primary outcome was VA after 16 weeks of refractive correction alone and final VA after 16 weeks of patching. Results The mean (SD) baseline VA in the amblyopic eye was 0.96 (0.27) logMAR, which improved to a mean (SD) of 0.84 (0.24) logMAR with refractive correction and to a mean (SD) of 0.71 (0.30) logMAR after the addition of patching (P < .001). Comparing the final VA with the baseline VA, we found that VA improvement averaged 2.59 lines. The final VA in the amblyopic eye was associated with the baseline VA in the amblyopic eye (P < .001), the magnitude of anisometropia (P < .001), and the level of patching compliance (P = .04). The improvement in VA with patching was inversely associated with participants' age (P = .03) and presence of eccentric fixation (P = .02). Conclusion Both refractive correction and patching significantly improved the VA of the amblyopic eye associated with myopic anisometropia, with 88% of participants' eyes improving 2 lines or more. Further improvement in VA was observed when patching plus near activities was added to refractive correction and patients were followed for 16 more weeks. We recommend that clinicians treat myopic anisometropic amblyopia with refractive correction and patching plus near activities.

Comparison of Screening Procedures in Hydroxychloroquine Toxicity [Clinical Sciences]

Objectives To compare different screening procedures for hydroxychloroquine sulfate (Plaquenil) toxicity at different stages of damage. Methods Ten patients were studied using 10-2 automated fields, multifocal electroretinography, spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence. Results All 10 patients used hydroxychloroquine for more than 6 years, and those with severe toxicity had been overdosed. Fundus examination findings were normal except for the patients with severe toxicity. All the patients showed parafoveal field loss, but this was sometimes subtle. Multifocal electroretinography demonstrated parafoveal weakness in the milder cases. The SD-OCT subfield thickness plots showed a ring of parafoveal thinning in all the patients. The SD-OCT cross-sections showed parafoveal loss of the inner segment–outer segment and cone outer segment tip lines at early stages of toxicity, progressing to parafoveal thinning of the outer nuclear layer and eventually to retinal pigment epithelium damage. There was a ring of autofluorescence in most patients. Conclusions Overdosage with hydroxychloroquine seemed a significant risk factor for toxicity. Different individuals were more or less sensitive to different tests. Fields can be sensitive but only if read with a low threshold for change. Hydroxychloroquine causes early parafoveal loss of the outer segment lines on SD-OCT, with the first changes often evident in the inferotemporal quadrant. Parafoveal thinning of the outer nuclear layer follows, before retinal pigment epithelium damage is visible. Careful screening with multiple tests can detect toxic damage before prominent loss of the outer nuclear layer.

Characterization of Limbal Stem Cell Deficiency by In Vivo Laser Scanning Confocal Microscopy: A Microstructural Approach [Clinical Sciences]

Objective To evaluate the cellular changes in the corneal epithelium and surrounding structures in limbal stem cell deficiency (LSCD) by using in vivo laser scanning confocal microscopy. Methods This was a prospective comparative study that included 27 eyes of 20 patients with LSCD and 12 eyes of 10 healthy subjects. All subjects underwent slitlamp examination, and LSCD was classified into 3 groups on the basis of clinical presentation. Confocal imaging of the central cornea and 4 locations of limbus was performed. Morphologic characteristics of the corneal epithelium were studied. The basal epithelial cell density and subbasal nerve density in the central cornea were calculated, and a potential correlation between the decrease in basal epithelial cell density and subbasal nerve density in LSCD was investigated. Results The wing and basal epithelial cells became progressively metaplastic, and the basal epithelial cell density and subbasal nerve density in the early and intermittent stages decreased significantly compared with controls (all P < .01). Normal basal epithelial cell morphology was completely lost and subbasal nerves were absent in the late stage of LSCD. The decrease in basal cell density correlated with the decrease in subbasal nerve density in patients with LSCD (P = .03). Conclusions There are significant microstructural changes associated with early LSCD. These cellular changes could help to understand the disease process and classify and monitor limbal stem cell dysfunction.

Evaluation of Visual Acuity Measurements After Autorefraction vs Manual Refraction in Eyes With and Without Diabetic Macular Edema [Clinical Sciences]

Objective To compare visual acuity (VA) scores after autorefraction vs manual refraction in eyes of patients with diabetes mellitus and a wide range of VAs. Methods The letter score from the Electronic Visual Acuity (EVA) test from the electronic Early Treatment Diabetic Retinopathy Study was measured after autorefraction (AR-EVA score) and after manual refraction (MR-EVA score), which is the research protocol of the Diabetic Retinopathy Clinical Research Network. Testing order was randomized, study participants and VA examiners were masked to refraction source, and a second EVA test using an identical supplemental manual refraction (MR-EVAsuppl score) was performed to determine test-retest variability. Results In 878 eyes of 456 study participants, the median MR-EVA score was 74 (Snellen equivalent, approximately 20/32). The spherical equivalent was often similar for manual refraction and autorefraction (median difference, 0.00; 5th-95th percentile range, –1.75 to 1.13 diopters). However, on average, the MR-EVA scores were slightly better than the AR-EVA scores, across the entire VA range. Furthermore, the variability between the AR-EVA scores and the MR-EVA scores was substantially greater than the test-retest variability of the MR-EVA scores (P < .001). The variability of differences was highly dependent on the autorefractor model. Conclusions Across a wide range of VAs at multiple sites using a variety of autorefractors, VA measurements tend to be worse with autorefraction than manual refraction. Differences between individual autorefractor models were identified. However, even among autorefractor models that compare most favorably with manual refraction, VA variability between autorefraction and manual refraction is higher than the test-retest variability of manual refraction. The results suggest that, with current instruments, autorefraction is not an acceptable substitute for manual refraction for most clinical trials with primary outcomes dependent on best-corrected VA.

Prevalence of and Risk Factors for Age-Related Macular Degeneration in a Multiethnic Asian Cohort [Epidemiology]

Objective To describe the prevalence of and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. Methods In this population-based study, 3172 persons of Chinese, Malay, and Indian ethnicities 40 years and older were included. Participants underwent comprehensive systemic and ocular examination, retinal photography, and laboratory investigations. Early and late AMD signs were graded from retinal photographs. Age-standardized prevalence estimates were calculated using the 2010 Singapore adult population as the standard population. Association with a range of systemic risk factors was analyzed. Results Of 3172 participants, AMD was present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons 40 years and older. The age-standardized prevalence was similar in all 3 Asian ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The prevalence increased with age and was higher in men. Of the range of risk factors evaluated, only myopic refractive error (<–0.5 D) was significantly associated with a lower risk for AMD (odds ratio, 0.44; P < .001, compared with emmetropia) in Chinese men. Conclusions The prevalence of AMD was similar in the 3 major ethnic groups in Asia and comparable with white populations. Myopic refractive error was associated with reduced risk of AMD in Chinese men.

Three-Year Outcomes of the Surgery for Trichiasis, Antibiotics to Prevent Recurrence Trial [Clinical Trial]

Objective To determine whether treatment with oral azithromycin compared with topical tetracycline reduces the recurrence of trichiasis for up to 3 years following surgery for trichiasis. Methods The Surgery for Trichiasis, Antibiotics to Prevent Recurrence (STAR) trial is a randomized, single-masked, clinical trial conducted in southern Ethiopia, a region where trachoma is hyperendemic. A total of 1452 patients who underwent trichiasis surgery were randomly assigned at a 2:1 ratio to either a single dose of oral azithromycin (1 g) or topical tetracycline (twice per day for 6 weeks) following surgery. Main Outcome Measures Recurrence of trichiasis within 3 years following surgery. Results The rate of recurrence was 10% in the azithromycin group and 13% in the tetracycline group. The azithromycin group had a 22% reduction in recurrence of trichiasis 3 years after surgery compared with the tetracycline group (P = .13). Severity of entropion at baseline was the most significant predictor of recurrence of trichiasis at 3 years. Conclusion Trichiasis recurrence rates in the STAR trial remained low for up to 3 years following surgery. The protective effect of a single dose of azithromycin was less than at 1 year and, although not statistically significant, was still suggestive up to 3 years following trichiasis surgery. Application to Clinical Practice A single dose of azithromycin after surgery remains an integral component of the World Health Organization's strategy for the elimination of trachoma by the year 2020. Trial Registration clinicaltrials.gov Identifier: NCT00347776.

Three-dimensional Distribution of the Vitelliform Lesion, Photoreceptors, and Retinal Pigment Epithelium in the Macula of Patients With Best Vitelliform Macular Dystrophy [Ophthalmic Molecular Genetics]

Objective To describe the anatomical phenotypes of Best vitelliform macular dystrophy (BVMD) with spectral-domain optical coherence tomography (SD-OCT) in a large series of patients with confirmed mutations in the BEST1 gene. Methods In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene. Color fundus photographs and SD-OCT images were evaluated and compared with those of 15 age-matched controls (30 eyes). Using a validated 3-dimensional SD-OCT segmentation algorithm, we calculated the equivalent thickness of photoreceptors and the equivalent thickness of the retinal pigment epithelium for each patient. The photoreceptor equivalent thickness and the retinal pigment epithelium (RPE) equivalent thickness were compared in all patients, in a region of the macula outside the central lesion for patients with BVMD and outside the fovea in control patients. Paired t tests were used for statistical analysis. Results The SD-OCT findings revealed that the vitelliform lesion consists of material above the RPE and below the outer segment tips. Additionally, drusen-like deposition of sub-RPE material was notable, and several patients exhibited a sub-RPE fibrotic nodule. Patients with BVMD had a mean photoreceptor equivalent thickness of 28.3 μm, and control patients had a mean photoreceptor equivalent thickness of 21.8 μm, a mean difference of 6.5 μm (P < .01), whereas the mean RPE equivalent thickness was not statistically different between patients with BVMD and control patients (P = .53). Conclusions The SD-OCT findings suggest that vitelliform material is located in the subretinal space and that BVMD is associated with diffuse photoreceptor outer segment abnormalities overlying a structurally normal RPE. Clinical Relevance These findings provide new insight into the pathophysiology of BVMD and thus have implications for the development of therapeutic interventions.

Retinal Microvascular Signs and Disability in the Cardiovascular Health Study [Epidemiology]

Objective To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL). Design Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction. Results During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1% vs 7.1%; adjusted hazard ratio, 1.45; 95% confidence interval, 1.24-1.69; P < .001). There was no evidence of interaction by advanced carotid atherosclerosis (P > .10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging. Conclusions These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.

Glaucoma-Related Adverse Events in the Infant Aphakia Treatment Study: 1-Year Results [Clinical Sciences]

Objectives To report the incidence of glaucoma and glaucoma suspects in the IATS, and to evaluate risk factors for the development of a glaucoma-related adverse event in patients in the IATS in the first year of follow-up. Methods A total of 114 infants between 1 and 6 months of age with a unilateral congenital cataract were assigned to undergo cataract surgery either with or without an intraocular lens implant. Standardized definitions of glaucoma and glaucoma suspect were created and used in the IATS. Results Of these 114 patients, 10 (9%) developed glaucoma and 4 (4%) had glaucoma suspect, for a total of 14 patients (12%) with a glaucoma-related adverse event in the treated eye through the first year of follow-up. Of the 57patients who underwent lensectomy and anterior vitrectomy, 5 (9%) developed a glaucoma-related adverse event; of the 57 patients who underwent an intraocular lens implant, 9 (16%) developed a glaucoma-related adverse event. The odds of developing a glaucoma-related adverse event were 3.1 times higher for a child with persistent fetal vasculature and 1.6 times higher for each month of age younger at cataract surgery. Conclusions Modern surgical techniques do not eliminate the early development of glaucoma following congenital cataract surgery with or without an intraocular lens implant. Younger patients with or without persistent fetal vasculature seem more likely to develop a glaucoma-related adverse event in the first year of follow-up. Vigilance for the early development of glaucoma is needed following congenital cataract surgery, especially when surgery is performed during early infancy or for a child with persistent fetal vasculature. Five-year follow-up data for the IATS will likely reveal more glaucoma-related adverse events. Trial Registration clinicaltrials.gov Identifier: NCT00212134

Prevention and Management of Graft Detachment in Descemet Membrane Endothelial Keratoplasty [Clinical Sciences]

Objective To describe the prevention and management of various types of graft detachment after Descemet membrane endothelial keratoplasty. Methods In 150 consecutive eyes that underwent Descemet membrane endothelial keratoplasty, the incidence and type of graft detachment were studied at 1, 3, 6, 9, 12, and 24 months after surgery in a nonrandomized, prospective clinical study at a tertiary referral center. Four groups of detachments were identified: a partial detachment of one-third or less of the graft surface area (n = 16; group 1); a partial detachment of more than one-third of the graft surface area (n = 8; group 2); a graft positioned upside down (n = 4; group 3); and a free-floating Descemet roll in the host anterior chamber (n = 8; group 4). Results Partial or complete graft detachment was found in 36 cases (24%), of which 18 (12%) were clinically significant. All 24 eyes with a partial detachment (groups 1 and 2) showed spontaneous corneal clearance, and all but 6 of these eyes (75%) reached visual acuity of 20/40 or better (≥0.5). A reversed clearance pattern and interface spikes were observed in eyes with the graft positioned upside down (group 3). Eyes with a free-floating graft (group 4) showed persistent corneal edema. Detachments were associated with inward folds (12 eyes [33%]), insufficient air-bubble support (7 eyes [19%]), upside-down graft positioning (4 eyes [11%]), use of plastic materials (2 eyes [6%]), irido-graft synechiae (1 eye [3%]), poor endothelial morphology (1 eye [3%]), and stromal irregularity under the main incision (1 eye [3%]); 14 (58%) of the partial detachments were localized inferiorly. Conclusions Awaiting spontaneous clearance may be advocated in eyes with a partial detachment. Minor adjustments in surgical protocol as well as careful patient selection may further reduce the incidence of graft detachment after Descemet membrane endothelial keratoplasty to 4% or less. Trial Registration clinicaltrials.gov Identifier: NCT00521898

Centrifugal Expansion of Fundus Autofluorescence Patterns in Stargardt Disease Over Time [Clinical Sciences]

Objective To study the longitudinal changes in autofluorescence in Stargardt disease to reveal aspects of disease progression not previously evident. Changes in autofluorescence reflect changing fluorophore compositions of lipofuscin and melanin in retinal pigment epithelial cells, which has been hypothesized to contribute to Stargardt disease pathogenesis. Methods We examined the temporospatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence) and 795 nm (near-infrared autofluorescence) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up, 11-57 months; mean, 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations. Results Longitudinal fundus autofluorescence imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were nonrandom and followed a radial path that left behind a trail of diminishing autofluorescence. Longitudinal near-infrared autofluorescence imaging also demonstrated centrifugal lesion spread but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. Fundus autofluorescence and near-infrared autofluorescence abnormalities were spatially correlated with each other, and together they reflect systematic progressions in fleck distribution and fluorophore composition occurring during the natural history of the disease. Conclusions Stargardt disease fleck lesions do not evolve randomly in location but instead follow consistent patterns of radial expansion and a systematic decay of autofluorescence that reflect changing lipofuscin and melanin compositions in retinal pigment epithelial cells. These progressive foveal-to-peripheral changes are helpful in elucidating molecular and cellular mechanisms underlying Stargardt disease and may constitute potential outcome measures in clinical trials.

Cataract Surgery After Trabeculectomy: The Effect on Trabeculectomy Function [Clinical Sciences]

Objective To determine whether the timing of cataract surgery after trabeculectomy has an effect on trabeculectomy function in terms of intraocular pressure control. Methods This was a cohort study nested within a randomized clinical trial. There were 235 participants with glaucoma who had a single previous trabeculectomy augmented with either intraoperative 5-fluorouracil or placebo. Cataract surgery with intraocular lens implantation was performed on participants judged to have significant lens opacity. Cox regression was performed to evaluate the effect of time between trabeculectomy and cataract surgery on the time to trabeculectomy failure, after adjusting for other relevant risk factors. The main outcome measure was time to failure of trabeculectomy, defined as an intraocular pressure of greater than 21 mm Hg. Results Of the 235 participants, 124 (52.7%) underwent subsequent cataract surgery. The median time from trabeculectomy to cataract surgery for these patients was 21.7 months (range, 4.6-81.9 months). The median follow-up period was 60 months (range, 28-84 months) for the cataract surgery group and 48 months (range, 12-84 months) for the non–cataract surgery group. Cox regression showed that the time from trabeculectomy to cataract surgery was significantly associated with time to trabeculectomy failure (hazard ratio, 1.73 [95% CI, 1.05-2.85]; P = .03). The adjusted declining hazard ratios for risk of subsequent trabeculectomy failure when cataract surgery was performed 6 months, 1 year, and 2 years after trabeculectomy were 3.00 (95% CI, 1.11-8.14), 1.73 (95% CI, 1.05-2.85), and 1.32 (95% CI, 1.02-1.69), respectively. Conclusions Cataract surgery after trabeculectomy increases the risk of trabeculectomy failure, and this risk is increased if the time between trabeculectomy and cataract surgery is shorter.

Corticosteroids for Bacterial Keratitis: The Steroids for Corneal Ulcers Trial (SCUT) [Clinical Trial]

Objective To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers. Methods Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization. Main Outcome Measures The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation. Results Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (–0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, –0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, –0.31 to –0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (–0.37 to –0.04; P = .02). Conclusions We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers. Application to Clinical Practice Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. Trial Registration clinicaltrials.gov Identifier: NCT00324168

The Steroids for Corneal Ulcers Trial: Study Design and Baseline Characteristics [Clinical Sciences]

Objectives To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. Methods Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbiological results, and patient demographics, for patients enrolled in the trial. Results Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P = .04) and deeper infiltrates (P = .04) and were more likely to be localized centrally (P = .002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n = 366, 72%). Conclusions The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. Trial Registration clinicaltrials.gov Identifier: NCT00324168

About This Journal [About This Journal]

Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations: Safety and Efficacy in 15 Children and Adults Followed Up to 3 Years [Clinical Trial]

Objective To determine the safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying the RPE65 gene. Design Open-label, dose-escalation phase I study of 15 patients (range, 11-30 years of age) evaluated after subretinal injection of the rAAV2- RPE65 vector into the worse-functioning eye. Five cohorts represented 4 dose levels and 2 different injection strategies. Main Outcome Measures Primary outcomes were systemic and ocular safety. Secondary outcomes assayed visual function with dark-adapted full-field sensitivity testing and visual acuity with Early Treatment Diabetic Retinopathy Study charts. Further assays included immune responses to the vector, static visual fields, pupillometry, mobility performance, and optical coherence tomography. Results No systemic toxicity was detected; ocular adverse events were related to surgery. Visual function improved in all patients to different degrees; improvements were localized to treated areas. Cone and rod sensitivities increased significantly in the study eyes but not in the control eyes. Minor acuity improvements were recorded in many study and control eyes. Major acuity improvements occurred in study eyes with the lowest entry acuities and parafoveal fixation loci treated with subretinal injections. Other patients with better foveal structure lost retinal thickness and acuity after subfoveal injections. Conclusions Gene therapy for Leber congenital amaurosis caused by RPE65 mutations is sufficiently safe and substantially efficacious in the extrafoveal retina. There is no benefit and some risk in treating the fovea. No evidence of age-dependent effects was found. Our results point to specific treatment strategies for subsequent phases. Application to Clinical Practice Gene therapy for inherited retinal disease has the potential to become a future part of clinical practice. Trial Registration clinicaltrials.gov Identifier: NCT00481546

Emergency Department Eye Care in Florida: A Study of Principal Payer Sources 2005 Through 2009 [Clinical Sciences]

Objective To describe trends in health insurance coverage for emergency department (ED) eye care in Florida from January 1, 2005, through December 31, 2009. Methods The Florida Agency for Health Care Administration ED data sets for ED outpatient visits and ED admissions for eye care were analyzed for type of insurance coverage and stratified according to age younger than 18 years and 18 years or older. Negative binomial regression models were used to measure the percentage of change in payer distribution for each 1-year increase in calendar year. Results During the 5-year study period, commercial insurance was the most frequent payer of ED outpatient services (31.1%), followed by self-pay (26.2%) and Medicaid (22.0%). For persons younger than 18 years, Medicaid and self-payment made up 67.7% of principal payers. For outpatient ED visits, the percentage of change in Medicaid increased 5.9% for each calendar year (P < .001) and commercial coverage declined 4.5% (P < .001 ). The proportion of Florida residents receiving Medicaid during the study period was less than the national average. Conclusions A substantial proportion of ED eye care in Florida is reimbursed through Medicaid or is paid for out of pocket. How the Patient Protection and Affordable Care Act of 2010 and the national economic recovery will affect safety-net institutions such as EDs and hospital staff is speculative, but the effect could be substantial.

Postoperative Visual Acuity in Patients With Fuchs Dystrophy Undergoing Descemet Membrane-Stripping Automated Endothelial Keratoplasty: Correlation With the Severity of Histologic Changes [Clinical Sciences]

Objective To investigate a correlation between the severity of histologic changes of the Descemet membrane in patients with Fuchs endothelial dystrophy and the best-corrected visual acuity (VA) after Descemet membrane–stripping automated endothelial keratoplasty (DSAEK). Methods In a retrospective study design, we created a histologic grading system based on common characteristics observed histologically among 92 DSAEK specimens sent to the University of Wisconsin Eye Pathology Laboratory with a clinical diagnosis of Fuchs dystrophy from 3 separate corneal surgeons. Cases were graded as mild, moderate, or severe on the basis of guttae dispersion, presence of a laminated Descemet membrane, presence of embedded guttae, and density of guttae. Regression models were built to study the relationship among preoperative VA, histologic findings, and best-corrected VA 6 months and 1 and 2 years after DSAEK. Results No correlation was found between the severity of histologic changes of Descemet membrane and preoperative VA. However, a correlation was noted between the preoperative and final VA. Cases with a laminated Descemet membrane but no embedded guttae (n = 8) appeared to be less responsive to DSAEK. Otherwise, the severity of histologic changes of Descemet membrane observed in patients with Fuchs corneal dystrophy after DSAEK did not show a statistically significant correlation with final VA. Conclusions Our analysis fails to show an inverse relationship between the severity of histologic changes of the Descemet membrane and the best-corrected VA of at least 20/40 after DSAEK for Fuchs endothelial dystrophy. However, in a subset of patients with Fuchs dystrophy who develop a laminated Descemet membrane without embedded guttae, the visual recovery after DSAEK is less than expected. The laminated architecture of Descemet membrane without embedded guttae may facilitate separation between the membrane layers and, thus, incomplete removal of the recipient's Descemet membrane during DSAEK, which may then limit the postoperative visual outcome.

August 2011 Archives Web Quiz Winner [Archives Web Quiz Winner]

New Grading System to Improve the Surgical Outcome of Multirecurrent Pterygia [Clinical Sciences]

Objective To report a new grading system and surgical outcome by sealing the gap between the conjunctiva and Tenon capsule. Methods A total of 32 eyes of 30 patients with pterygia were managed at the Ocular Surface Center from January 1, 2002, through December 31, 2010. The eyes were consecutively operated on by recession; sealing of the gap; covering of exposed medial rectus muscle by amniotic membrane, conjunctival autograft, or oral mucosal graft (OMG); and covering of the bare sclera with amniotic membrane. Main outcome measures were recurrence, diplopia, and caruncle morphological characteristics. Results Caruncle grading strongly correlated with residual conjunctiva (P = .01), severity of diplopia (P = .001), and overall success rate (P = .05). Amniotic membrane transplantation alone was successful in 23 eyes with residual conjunctiva of 27.8 (10.1) mm, which was significantly longer than those in 6 cases in which amniotic membrane transplantation failed (13.1 [11.4] mm, P = .007) and those in 8 cases in which amniotic membrane transplantation was successful but that required an additional conjunctival autograft or oral mucosal graft (10.9 [10.4] mm, P = .001). During mean (SD) follow-up of 27.5 (20.5) months, 30 of 32 eyes (94%) achieved total success without recurrence and diplopia and normal caruncle in 17 of 21 eyes (81%) with abnormal caruncle before surgery. One eye (3%) developed corneal recurrence and was lost to follow-up, and 1 eye (3%) was left with a depressed caruncle and residual diplopia on adduction. Conclusions Caruncle morphological characteristics and residual conjunctiva measurement help grade the severity of recurrent pterygium, guide surgical techniques, and predict outcomes. Sealing of the gap is important to create a strong barrier for preventing recurrence, restoring caruncle morphological characteristics, and regaining full motility in multirecurrent pterygia.

Multimodality Diagnostic Imaging in Unilateral Acute Idiopathic Maculopathy [Clinical Sciences]

Objective To describe the clinical features and imaging characteristics in unilateral acute idiopathic maculopathy. Methods Retrospective review of 4 patients with a diagnosis of unilateral acute idiopathic maculopathy. Clinical characteristics (age, symptoms, Snellen visual acuity, and funduscopic features) and images from spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were analyzed. Results The median (range) age at presentation was 31 (27-52) years. The median (range) interval between symptom onset and presentation was 4 (1-20) weeks. Associated systemic findings included a viral prodrome (50%), orchitis (50%), hand-foot-mouth disease (25%), and positive coxsackievirus titers (50%). The median (range) visual acuity at initial examination was 20/400 (20/70 to 1/400), which improved to 20/30 (20/20 to 20/60) at final follow-up. The median (range) follow-up time was 8 (8-13) weeks. Early in the disease course, the central macula developed irregular, circular areas of white-gray discoloration. Following recovery, the macula had a stippled retinal pigment epithelium characterized by rarefaction and hyperplasia. Fluorescein angiography demonstrated irregular early hyperfluorescence and late subretinal hyperfluorescence. Spectral-domain optical coherence tomography showed a partially reversible disruption of the outer photoreceptor layer. Fundus autofluorescence initially revealed stippled autofluorescence that eventually became more hypoautofluorescent. Indocyanine green angiography showed "moth-eaten"–appearing choroidal vasculature, suggestive of choroidal inflammation. Conclusions The imaging characteristics highlight the structural changes during the active and resolution phases of unilateral acute idiopathic maculopathy. The visual recovery correlates with structural changes and suggests that the pathogenesis involves inflammation of the inner choroid, retinal pigment epithelium, and outer photoreceptor complex that is partially reversible.

Clinical and Pathologic Characteristics of Biopsy-Proven Iris Melanoma: A Multicenter International Study [Clinical Sciences]

Objective To collaborate with multiple centers to identify representative epidemiological, clinical, and pathologic characteristics of melanoma of the iris. This international, multicenter, Internet-assisted study in ophthalmic oncology demonstrates the collaboration among eye cancer specialists to stage and describe the clinical and pathologic characteristics of biopsy-proven melanoma of the iris. Methods A computer program was created to allow for Internet-assisted multicenter, privacy-protected, online data entry. Eight eye cancer centers in 6 countries performed retrospective chart reviews. Statistical analysis included patient and tumor characteristics, ocular and angle abnormalities, management, histopathology, and outcomes. Results A total of 131 patients with iris melanoma (mean age, 64 years [range, 20-100 years]) were found to have blue-gray (62.2%), green-hazel (29.1%), or brown (8.7%) irides. Iris melanoma color was brown (65.6%), amelanotic (9.9%), and multicolored (6.9%). A mean of 2.5 clock hours of iris was visibly involved with melanoma, typically centered at the 6-o’clock meridian. Presentations included iritis, glaucoma, hyphema, and sector cataract. High-frequency ultrasonography revealed a largest mean tumor diameter of 4.9 mm, a mean maximum tumor thickness of 1.9 mm, angle blunting (52%), iris root disinsertion (9%), and posterior iris pigment epithelium displacement (9%). Using the American Joint Commission on Cancer–International Union Against Cancer classification, we identified 56% of tumors as T1, 34% of tumors as T2, 2% of tumors as T3, and 1% of tumors as T4. Histopathologic grades were G1-spindle (54%), G2-mixed (28%), G3-epithelioid (5%), and undetermined (13%) cell types. Primary treatment involved radiation (26%) and surgery (64%). Kaplan-Meier analysis found a 10.7% risk of metastatic melanoma at 5 years. Conclusions Iris melanomas were most likely to be brown and found in the inferior quadrants of patients with light irides. Typically small and unifocal, melanomas are commonly associated with angle blunting and spindle cell histopathology. This multicenter, Internet-based, international study successfully pooled data and extracted information on biopsy-proven melanoma of the iris.

Functional and Anatomic Consequences of Subretinal Dosing in the Cynomolgus Macaque [Laboratory Sciences]

Objective To characterize functional and anatomic sequelae of a bleb induced by subretinal injection. Methods Subretinal injections (100 µL) of balanced salt solution were placed in the superotemporal macula of 1 eye in 3 cynomolgus macaques. Fellow eyes received intravitreal injections (100 µL) of balanced salt solution. Fundus photography, ocular coherence tomography, and multifocal electroretinography were performed before and immediately after injection and again at intervals up to 3 months postinjection. Histopathologic analyses included transmission electron microscopy and immunohistochemistry for glial fibrillary acidic protein, rhodopsin, M/L-cone opsin, and S-cone opsin. Results Retinas were reattached by 2 days postinjection (seen by ocular coherence tomography). Multifocal electroretinography waveforms were suppressed post–subretinal injection within the subretinal injection bleb and, surprisingly, also in regions far peripheral to this area. Multifocal electroretinography amplitudes were nearly completely recovered by 90 days. The spectral-domain ocular coherence tomography inner segment–outer segment line had decreased reflectivity at 92 days. Glial fibrillary acidic protein and S-cone opsin staining were unaffected. Rhodopsin and M/L-cone opsins were partially displaced into the inner segments. Transmission electron microscopy revealed disorganization of the outer segment rod (but not cone) discs. At all postinjection intervals, eyes with intravitreal injection were similar to baseline. Conclusions Subretinal injection is a promising route for drug delivery to the eye. Three months post–subretinal injection, retinal function was nearly recovered, although reorganization of the outer segment rod disc remained disrupted. Understanding the functional and anatomic effects of subretinal injection is important for interpretation of the effects of compounds delivered to the subretinal space. Clinical Relevance Subretinal injection is a new potential route for drug delivery to the eye. Separating drug effects from the procedural effects is critical.

Recovery of Corneal Sensitivity, Calcitonin Gene-Related Peptide-Positive Nerves, and Increased Wound Healing Induced by Pigment Epithelial-Derived Factor Plus Docosahexaenoic Acid After Experimental Surgery [Laboratory Sciences]

Objective To assess function of regenerated corneal nerves in correlation with epithelial wound healing after experimental nerve damage in rabbits treated with pigment epithelial–derived factor (PEDF) plus docosahexaenoic acid (DHA). Methods An 8-mm stromal dissection was performed in the right eyes of adult New Zealand rabbits. Treatment with PEDF+DHA was for 6 weeks. Corneal sensation was measured weekly by Cochet-Bonnet esthesiometer. After 8 weeks, immunofluorescence with βIII-tubulin, calcitonin gene-related peptide, and substance P antibodies was performed to quantify nerves. Also, rabbits were treated with PEDF+DHA for 4 weeks after lamellar keratectomy, followed by 8-mm epithelial debridement and epithelial defect assessment. One week after surgery, corneas were stained with anti-Ki67 antibody to assess cell proliferation. Results Eight weeks after surgery, calcitonin gene-related peptide–positive nerve fibers in the PEDF+DHA group were similar to normal rabbit corneas but were decreased in the vehicle. Substance P was localized in the subepithelial plexus but appeared in epithelial cells after nerve injury regardless of treatment. Five weeks after surgery, an increase in corneal sensitivity occurred in the PEDF+DHA group and reached normal values by 8 weeks. Pigment epithelial–derived factor plus DHA increased epithelial wound healing after lamellar keratectomy. One week after epithelial injury, Ki67-positive cells increased in the limbal area. Conclusion Pigment epithelial–derived factor plus DHA promotes regeneration of calcitonin gene-related peptide–positive corneal nerves, accelerating wound healing and return of corneal sensitivity. Clinical Relevance Pigment epithelial–derived factor plus DHA represents a new approach to regenerate nerves and a potential treatment for prevention of severe dry eye after surgery or diseases of the ocular surface.

Blockade of Prolymphangiogenic Vascular Endothelial Growth Factor C in Dry Eye Disease [Laboratory Sciences]

Objective To determine whether blocking prolymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) would suppress alloimmunity in dry eye disease using a murine model. Methods The effects of intraperitoneal injections of 400 μg of anti–VEGF-C antibody (treated group) and intraperitoneal normal saline (untreated group) were studied in murine dry eyes induced by exposing mice to high-flow desiccated air in a controlled-environment chamber. Growth of lymphatic vessels and infiltration of macrophages were evaluated by immunohistochemistry using CD31 (panendothelial marker), lymphatic vessel endothelial receptor 1 (lymphatic endothelial marker), and CD11b (monocyte and macrophage marker). Real-time polymerase chain reaction was performed to quantify expression of different inflammatory cytokine transcripts in the conjunctiva and lymph nodes as well as vascular endothelial growth factors and their receptors (VEGF-A, VEGF-C, VEGF-D, VEGFR-2, and VEGFR-3) in the cornea. Results Blocking VEGF-C led to significant reductions in lymphatic caliber (P = .02) and lymphatic area (P = .006) in the corneas of mice with dry eye disease. In addition to significantly decreasing CD11b+ cells (P = .005), anti–VEGF-C treatment significantly decreased transcript levels of VEGF-C (P = .002), VEGF-D (P = .01), and VEGFR-3 (P = .02) in the corneas of the treated group. A significant decrease in expression of inflammatory cytokines in the conjunctiva (interleukin 1α, P = .003; interleukin 1β, P = .02; interleukin 6, P = .005) and lymph nodes (interferon , P = .008; interleukin 17, P = .003) was also seen with anti–VEGF-C treatment. Conclusion Treatment with anti–VEGF-C led to significant improvement in dry eye disease, reflected by a decrease in inflammation at the clinical, molecular, and cellular levels. Clinical Relevance Targeting prolymphangiogenic growth factors or their receptors could inhibit the trafficking of antigen-presenting cells to the draining lymph nodes and hence prove to be a potential therapeutic target for dry eye disease.

Dry Eye Disease: An Immune-Mediated Ocular Surface Disorder [Mechanisms of Ophthalmic Disease]

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management.

Capsule Membrane Suture Fixation of Decentered Sulcus Intraocular Lenses [Surgical Technique]

Different surgical methods are used to fixate the subluxated sulcus intraocular lens (IOL) in the absence of in-bag fixation, ranging from iris and scleral suturing to optic capture of the IOL. A new technique, which we have termed capsule membrane suture fixation, provides an additional method for securing a subluxated or decentered sulcus-based IOL to the remnant capsule or a capsular membrane. This method can also be used in secondary surgery for fixation, repositioning, or removal and replacement of IOLs. In this technique, the IOL haptics are sutured to the fibrotic elements of the capsular membrane to center and secure the IOL to the capsular membrane and prevent complications associated with uveal touch.

Emergency Department Use for Eye Care Services and Future Directions in Care [Editorial]

The Role of Antiviral Therapy After the Resolution of Acute Herpes Simplex Keratitis or Acute Herpes Zoster Ophthalmicus [Editorial]

Interview With Thaddeus P. Dryja, MD [Lessons in Leadership]

Polymerase Chain Reaction-Based Ganciclovir Resistance Testing of Ocular Fluids for Cytomegalovirus Retinitis [Small Case Series]

Population Differences in Genetic Risk for Age-Related Macular Degeneration and Implications for Genetic Testing [Research Letters]

{beta}-Blocking and Racial Variation in the Severity of Retinopathy of Prematurity [Research Letters]

Epithelial Downgrowth After Type 1 Boston Keratoprosthesis Manifesting as Tractional Retinal Detachment and Epiretinal Membrane [Research Letters]

Bilateral Uveal Effusion and Angle-Closure Glaucoma Associated With Bupropion Use [Research Letters]

Small Dose of Rituximab for Graves Orbitopathy: New Insights Into the Mechanism of Action [Research Letters]

Risks of Adverse Events With Therapies for Age-Related Macular Degeneration: A Response [Letters]

Risks of Adverse Events With Therapies for Age-Related Macular Degeneration: A Response--Reply [Letters]

External Needle Drainage Device [Letters]

Intravitreal Inoculation of Cotton After Bevacizumab (Avastin) Injection [Ophthalmic Images]