The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19.

OBJECTIVE: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I125) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. DESIGN: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. METHODS: I125 brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. MAIN OUTCOME MEASURES: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. RESULTS: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). CONCLUSIONS: Local treatment failure and enucleation were relatively infrequent events after I125 brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.

VOLUMETRIC SINGLE-LAYER INNER RETINAL ANALYSIS IN PATIENTS WITH HYDROXYCHLOROQUINE TOXICITY.

PURPOSE: To compare retinal layer volumes using spectral-domain optical coherence tomography between eyes with hydroxychloroquine (HCQ) toxicity and control eyes. METHODS: Using a previously validated algorithm, volumetric analysis from the macular cube scan of the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina (outer plexiform layer to retinal pigment epithelium) layers were compared in three sets of patients: patients with a clinical diagnosis of HCQ toxicity, age-matched patients taking HCQ but not manifesting overt toxicity, and age-matched control patients. RESULTS: There were 14 patients in each group. The ganglion cell layer (P = 0.01), inner plexiform layer (P = 0.004), inner nuclear layer (P < 0.001), and outer plexiform layer to retinal pigment epithelium (P < 0.001) volumes were significantly reduced in HCQ toxicity eyes relative to the HCQ exposure eyes. There were no significant inner and outer retinal volume differences between the HCQ exposure group and group with no HCQ use (P > 0.05 for all layers). Increasing disease severity correlated with increasing volume loss in the inner retina (2.27 mm in early disease vs. 1.78 mm in advanced retinopathy, P = 0.02). CONCLUSION: Hydroxychloroquine toxicity seems to result in both outer and inner retinal volumetric thinning compared with age-matched control patients and patients taking HCQ but not manifesting toxicity.

Visual acuity changes in the preoperative period in patients undergoing cataract surgery.

OBJECTIVE: This study quantifies change in best visual acuity (BVA) over the preoperative period and assesses factors associated with postoperative outcomes. DESIGN: Retrospective chart review conducted at a single institution. PARTICIPANTS: A total of 691 patients underwent cataract surgery and had a preoperative assessment 0-30 days prior to surgery following their surgical evaluation. METHODS: Baseline demographics and past medical and clinical data were collected through electronic medical record query. BVA was noted at initial surgical evaluation, preoperative assessment, and nearest postoperative assessment. RESULTS: A total of 691 patients (911 eyes) were included with mean BVAs at the initial evaluation, preoperative assessment, and postoperative assessment of 68.3 ± 16.8, 64.6 ± 18.5, and 81.1 ± 12.0 ETDRS letters, respectively. Mean BVA was significantly higher postoperatively compared with the preoperative assessment and initial evaluation (p < 0.0001). There was a mean of 53.8 days between initial surgical evaluation and surgery date and a mean of 49.9 days between the preoperative assessment and initial surgical evaluation. The mean interval between the preoperative assessment and surgery was 11.7 days. In the preoperative period, 9.1% of eyes experienced worsening of BVA by >3 eyes and 0.9% experienced improvement of BVA by >3 lines. Time to surgery was significantly associated with change in postoperative BVA (effect size, -0.03 ETDRS letters; p = 0.015) but was not significant on multiple linear regression. BVA at initial evaluation, glaucoma, and glaucoma surgery were all significantly associated with postoperative outcomes. CONCLUSION: Most eyes experienced stable vision in the preoperative period for cataract surgery. On average, patients with high BVAs at the time of initial surgical evaluation may be able to defer surgery without the risk of poorer surgical outcomes.

Clinical Utility of Spectral-Domain Optical Coherence Tomography Marker Disorganization of Retinal Inner Layers in Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: Disorganization of retinal inner layers (DRIL) is a potential spectral-domain optical coherence tomography (SD-OCT) imaging biomarker with clinical utility in diabetic retinopathy (DR). PATIENTS AND METHODS: A cross-sectional study was conducted at a large academic center. The cohort was composed of 1,175 patients with type 2 diabetes with and without retinopathy on initial examination between September 2009 and January 2019 (n = 2,083 eyes). DR risk and progression factors were obtained from the medical record. Trained graders masked to patients' clinical histories evaluated SD-OCT scans for DRIL. RESULTS: Of 2,083 eyes, 28.1% (n = 585) demonstrated presence of DRIL with high interrater reliability (K = 0.88, 95% CI 0.86-0.90). DRIL was associated with worse visual acuity (VA) (P < 0.001) and DR severity (P < 0.0001). Insulin users had more severe DR (P < 0.0001). DR-related factors, race (Black, White) and sex (male) were significantly associated with DRIL (P < 0.05). CONCLUSIONS: DRIL was strongly associated with DR severity and worse VA, supporting its utility as an unfavorable prognostic indicator. [Ophthalmic Surg Lasers Imaging Retina 2023;54:692-700.].

Lessons learned: wrong intraocular lens.

OBJECTIVE: To report cases involving the placement of the wrong intraocular lens (IOL) at the time of cataract surgery where human error occurred. DESIGN: Retrospective small case series, convenience sample. PARTICIPANTS: Seven surgical cases. METHODS: Institutional review of errors committed and subsequent improvements to clinical protocols. MAIN OUTCOME MEASURES: Lessons learned and changes in procedures adapted. RESULTS: The pathways to a wrong IOL are many but largely reflect some combination of poor surgical team communication, transcription error, lack of preoperative clarity in surgical planning or failure to match the patient, and IOL calculation sheet with 2 unique identifiers. CONCLUSIONS: Safety in surgery involving IOLs is enhanced both by strict procedures, such as an IOL-specific "time-out," and the fostering of a surgical team culture in which all members are encouraged to voice questions and concerns.

Patient-Reported Complications after Intravitreal Injection and Their Predictive Factors.

PURPOSE: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. DESIGN: Retrospective, institutional review board-approved study. PARTICIPANTS: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. METHODS: Intravitreal injection. MAIN OUTCOME MEASURES: Complication occurrence within 15 days of injection. RESULTS: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. CONCLUSIONS: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.

A review of clinical trials of anti-VEGF agents for diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of vision loss in the working-age population worldwide. Many observational and preclinical studies have implicated vascular endothelial growth factor (VEGF) in the pathogenesis of DR, and recent successes with anti-VEGF therapy for age-related macular degeneration (AMD) have prompted research into the application of anti-VEGF drugs to DR. Here we review the numerous early studies that suggest an important potential role for anti-VEGF agents in the management of diabetic retinopathy. CONCLUSIONS: For diabetic macular edema, phase II trials of intravitreal pegaptanib and intravitreal ranibizumab have shown short-term benefit in visual acuity. Intravitreal bevacizumab also has been shown to have beneficial short-term effects on both visual acuity and retinal thickness. For proliferative diabetic retinopathy (PDR), early studies suggest that intravitreal bevacizumab temporarily decreases leakage from diabetic neovascular lesions, but this treatment may be associated with tractional retinal detachment (TRD). Furthermore, several studies indicate that bevacizumab is likely to prove a helpful adjunct to diabetic pars plana vitrectomy (PPV) for TRD. Finally, three small series suggest a potential beneficial effect of a single dose of bevacizumab to prevent worsening of DME after cataract surgery. Use of anti-VEGF medications for any of these indications is off-label. Despite promising early reports on the safety of these medications, we eagerly await the results of large, controlled trials to substantiate the safety and efficacy of anti-VEGF drugs for diabetic retinopathy.

Eplerenone for the treatment of chronic central serous chorioretinopathy: 3-year clinical experience.

BACKGROUND/AIMS: The efficacy of mineralocorticoid receptor antagonist eplerenone to treat chronic central serous chorioretinopathy (CSCR) has been established. However, previous studies have been limited by small cohort size and short follow-up duration. This study aims to report 3-year clinical outcomes of patients treated with eplerenone for chronic CSCR. METHODS: Institutional review board-approved retrospective chart analysis at a single institution from 2012 to 2018. Baseline best-corrected visual acuity and anatomical measurements related to degree of subretinal fluid (SRF) were collected at eplerenone initiation. Follow-up data were collected at the closest date to 12, 24 and 36 months. RESULTS: Data were obtained for 100 eyes of 83 patients at 1-year (mean 11.18 ± 4.00 months), 49 eyes at 2-year (24.01 ± 3.33 months) and 33 eyes at 3-year (mean 35.5 ± 7.89 months) follow-up visits. The rate of complete SRF resolution was 31%, 28% and 33%, respectively. At final follow-up, logarithm of the minimum angle of resolution visual acuity change from baseline was +0.10 ± 0.24 (p = 0.130). Average change from baseline at final follow-up for central subfield thickness was -97 ± 140.6 µm (p < 0.001), cube volume was -1.07 ± 1.71 mm3 (p < 0.001), macular thickness -28. 5 ± 47.5 µm (p < 0.001), maximum SRF height was -95.6 ± 160.5 µm (p < 0.001) and maximum SRF diameter was -1169.0 ± 1638.7 µm (p = 0.008). CONCLUSION: Anatomical improvement occurs primarily within the first year of eplerenone treatment for chronic CSCR.

Nine-year incidence of visual impairment in the Barbados Eye Studies.

OBJECTIVE: To describe the 9-year incidence of visual impairment and primary causes of blindness among black participants of the Barbados Eye Studies (BES). DESIGN: Population-based prospective cohort study. PARTICIPANTS: The BES followed a nationally representative cohort selected by simple random sampling, aged 40 to 84 years at baseline, with reexaminations after 4 years (Barbados Incidence Study of Eye Diseases [BISED]) and 9 years (BISED II). BISED II included 2793 (81%) of those eligible. METHODS: Cumulative 9-year incidence rates were estimated by the Product-Limit approach. The study was reviewed and approved by the institutional review boards of collaborating institutions. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA) was assessed by the Ferris-Bailey chart, following a modified Early Treatment of Diabetic Retinopathy Study protocol. Low vision and blindness were defined by World Health Organization (WHO) criteria as VA <6/18 to 6/120, and <6/120, respectively, in the better eye, and by U.S. criteria as VA < or =20/40 and < or =20/200, respectively. Vision loss was defined as a decrease of 15 letters or more read correctly in the better eye between baseline and follow-up examinations. RESULTS: The 9-year incidence was 1.0% and 2.1% for blindness and 6.0% and 9.0% for low vision, by WHO and U.S. criteria, respectively. Older age at baseline was associated with higher incidence of low vision and blindness, reaching 23.0% (95% confidence interval [CI], 18.8-28.0) and 4.3% (95% CI, 2.7-6.9) at age 70 years or more, based on WHO criteria. The primary causes of incident bilateral blindness (U.S. criteria) in 126 eyes were age-related cataract (48.3%), open-angle glaucoma (OAG) (14.3%), combined cataract and OAG (6.3%), diabetic retinopathy (8.7%), and optic atrophy (7.1%). Age-related macular degeneration (2.4%) rarely caused blindness. CONCLUSIONS: Incident visual impairment is exceedingly high in this population. Cataract, OAG, and diabetic retinopathy remain the major causes of blindness, underpinning the clinical and public health significance of these conditions in this and similar populations.

Detection of Choroidal Neovascular Membrane Beneath Pigment Epithelial Detachment Using SD-OCTA.

BACKGROUND AND OBJECTIVE: To identify choroidal neovascular membrane (CNVM) associated with spectral-domain optical coherence tomography (SD-OCT)-defined pigment epithelial detachment (PED) using SD-OCT angiography (SD-OCTA). PATIENTS AND METHODS: Sixty-nine patients with same-day OCT and OCTA imaging were reviewed, and 41 eyes of 29 patients with PEDs were included. OCTs were analyzed for PED type, fluid, and subretinal hyperreflective material (SHRM). RESULTS: Twenty-seven eyes (66%) demonstrated CNVM on OCTA beneath all subtypes of PED. Twenty-two eyes (75.9%) with fluid or SHRM demonstrated CNVM on OCTA (P = .036). Fluid corresponded in a statistically significant manner with treatment (P = .0032), whereas SHRM did not (P = .613). OCTA-defined CNVM showed borderline statistically significant correlation to treatment (P = .05). Increased choroidal flow signal seen in 50% of eyes did not demonstrate statistically significant correlation to the presence of fluid on SD-OCT (P = .2798) or treatment decision (P = .678). A subset of 14 untreated eyes with CNVM was analyzed, 21% of which required treatment at subsequent visits. CONCLUSIONS: OCTA-defined CNVM was seen in all subtypes of PED in clinically active and inactive disease. The role of OCTA in predicting need for treatment remains to be established. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:620-626.].

Vitamin usage patterns in the prevention of advanced age-related macular degeneration.

OBJECTIVE: To describe micronutrient usage patterns among patients at a tertiary ophthalmic center. DESIGN: Cross-sectional clinical case series. PARTICIPANTS: Three hundred thirty-two adult patients with a diagnosis of age-related macular degeneration (AMD). METHODS: Participants were surveyed about micronutrient usage patterns. The treating ophthalmologist recorded AMD severity using the Age-Related Eye Disease Study (AREDS) classification system. MAIN OUTCOME MEASURES: Responses to study questionnaire and level of AMD severity. RESULTS: Among 332 participants, 309 (93%) were using supplements, among which 174 (52%) supplemented with an AREDS-like formulation. Of these 174, 140 (80%) were considered AREDS supplement candidates based on study guidelines. Applying AREDS supplementation guidelines to the full cohort, 228 (69%) were candidates for supplementation. Only 140 (61%) of these individuals were confirmed to be using the correct formulation and dosage; an additional 13 (6%) used the AREDS formulation but were not using the recommended dosage. CONCLUSIONS: Among patients receiving care for AMD at a tertiary retinal center, more than one third of those deemed candidates for AREDS-type supplements were not using them or were using an incorrect dose. Furthermore, nearly one fifth of participants who were using high-dose supplements did not have a level of AMD anticipated to benefit from usage. Increased patient education is needed regarding the recommendations of AREDS.

Open-angle glaucoma and mortality: The Barbados Eye Studies.

OBJECTIVE: To evaluate the relationship between open-angle glaucoma (OAG) and mortality in a black population at 9-years' follow-up. DESIGN: Population-based cohort study of 4092 black participants (aged 40-84 years at baseline) in the Barbados Eye Studies. Open-angle glaucoma was defined by visual field defects and optic disc damage, based on standardized examinations and photograph gradings. Ocular hypertension was defined by an intraocular pressure greater than 21 mm Hg or treatment, without OAG damage. Mortality was ascertained from death certificates. Cox proportional hazards regression analyses determined associations with mortality. RESULTS: After 9 years, 764 (19%) participants were deceased. Mortality was unrelated to overall OAG at baseline (n = 300) after adjustment for confounders. However, cardiovascular mortality tended to increase in persons with previously diagnosed/treated OAG (n = 141; relative risk [RR], 1.38, P = .07) and was significantly higher with treatment involving timolol maleate (RR, 1.91, P = .04). Cardiovascular deaths also tended to increase in persons with ocular hypertension at baseline (n = 498; RR, 1.28, P = .06). CONCLUSIONS: In this black population, cardiovascular mortality tended to increase in persons with previously diagnosed/treated OAG and ocular hypertension. The excess mortality associated with timolol maleate treatment of OAG, also found in a white population, warrants further investigation.

Dark-Without-Pressure Lesion in a Patient in Their Mid-40s.

This case report discusses a diagnosis of a dark-without-pressure lesion in an otherwise asymptomatic patient in their mid-40s.