Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Surgical Approach for Monoclonal Gammopathy of Undetermined Significance-Related Ocular Copper Deposition.

PURPOSE: The aim of this study was to present the surgical management of a patient with ocular copper deposition associated with monoclonal gammopathy of undetermined significance (MGUS). METHODS: This is a case report of a 44-year-old man with MGUS who presented to us with bilateral diffuse deposition of copper in the cornea and lens. RESULTS: Despite initiating systemic therapy for MGUS, no corneal clearing was observed. A decision was made to proceed with cataract extraction in the left eye given worsening vision. Despite trypan blue staining and a central descemetorhexis, visualization remained too poor to complete phacoemulsification. Pars plana lensectomy and vitrectomy to remove the residual lens material and placement of a posterior chamber intraocular lens in the sulcus with endoillumination was subsequently performed. As vision in the left eye steadily improved postoperatively, cataract surgery was then performed in the right eye. With use of trypan blue, creation of a 6-mm central descemetorhexis, and a retinal light pipe for endoillumination anteriorly to augment visualization, capsulorhexis, phacoemulsification, and insertion of intraocular lens in the bag were completed without difficulty. The patient's vision improved at subsequent follow-ups, reaching a final best-corrected visual acuity of 20/20-1 in the right eye and 20/25-1 in the left eye. CONCLUSIONS: Ocular copper deposition is a rare manifestation of MGUS. Cataract extraction is challenging, often requiring advanced techniques. Endoillumination is useful to improve visualization through the dense corneal copper deposition.

Retinal characteristics in eyes with pathologic myopia among individuals self-identifying as Black.

OBJECTIVE: Investigate retinal characteristics of pathologic myopia (PM) among patients self-identifying as Black. DESIGN: Retrospective cohort single-institution retrospective medical record review. METHODS: Adult patients between January 2005 and December 2014 with International Classification of Diseases (ICD) codes consistent with PM and given 5-year follow-up were evaluated. The Study Group consisted of patients self-identifying as Black, and the Comparison Group consisted of those not self-identifying as Black. Ocular features at study baseline and 5-year follow-up visit were evaluated. RESULTS: Among 428 patients with PM, 60 (14%) self-identified as Black and 18 (30%) had baseline and 5-year follow-up visits. Of the remaining 368 patients, 63 were in the Comparison Group. For the study (n = 18) and Comparison Group (n = 29), median (25th percentile, 75th percentile) baseline visual acuity was 20/40 (20/25, 20/50) and 20/32 (20/25, 20/50) in the better-seeing eye and 20/70 (20/50, 20/1400) and 20/100 (20/50, 20/200), respectively, in the worse-seeing eye. In the eyes that did not have choroidal neovascularization (CNV) in the study and Comparison Group, median study baseline optical coherence tomography central subfield thickness was 196 µm (169, 306 µm) and 225 µm (191, 280 µm), respectively, in the better-seeing eye and 208 µm (181, 260 µm) and 194 µm (171, 248 µm), respectively, in the worse-seeing eye. Baseline prevalence of CNV was 1 Study Group eye (3%) and 20 Comparison Group eyes (34%). By the 5-year visit, zero (0%) and 4 (15%) additional eyes had CNV in the study and Comparison Group, respectively. CONCLUSION: These findings suggest that the prevalence and incidence of CNV may be lower in patients with PM self-identifying as Black when compared with individuals of other races.

Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration? A Prospective, Randomized, Pilot Study.

PURPOSE: To report findings when dilated fundus examination (DFE) is omitted from follow-up of patients receiving anti-VEGF injections for neovascular age-related macular degeneration (NVAMD). DESIGN: Randomized pilot study. PARTICIPANTS: NVAMD patients with two or more injections of anti-VEGF within prior six months who were expected to require treatment for at least eight more months. METHODS AND INTERVENTIONS: Participants were assigned to either retinal imaging and DFE or retinal imaging without a DFE except at 16 weeks and 32 weeks and at study completion. OUTCOMES: Primary safety outcomes were change in usual-corrected visual acuity (UCVA) and central subfield thickness (CST). Primary efficacy outcomes included time spent in clinic and patient satisfaction with clinic visits. RESULTS: The 66 participants had mean baseline UCVA of 20/50 in the study eye. Median change in UCVA from baseline to each clinic visit in each arm was "no change". Mean change in CST was less than 15 microns from baseline to any follow-up clinic visit. Time spent in the clinic at follow-up visits averaged 20 minutes less for participants in the Imaging Only group than those in the Full Exam group. More participants in the Imaging Only group were satisfied with the time spent in clinic and with the clinic visits overall than participants in the Full Exam group: means of 71 vs 91 minutes, respectively, per clinic visit. CONCLUSION: Based on findings from this randomized pilot study, follow-up retina clinic visits for established patients who have NVAMD and are under treatment with intravitreous injection of anti-VEGF agents could be streamlined by implementing longer intervals between DFE and by relying on imaging alone to make most decisions regarding the need for retreatment, thereby reducing the time spent by patients in clinic and increasing their satisfaction with care received, without excess adverse events. TRIAL REGISTRATION: NCT02251366.

Patient Use of Dietary Supplements, Home Monitoring, or Genetic Testing for Nonneovascular Age-Related Macular Degeneration.

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants' use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

BUCKLE-ASSOCIATED EPITHELIAL CYST MASQUERADING AS INTRAOCULAR INFLAMMATION.

BACKGROUND/PURPOSE: To describe a case of a rare, late scleral buckle-related complication, which was masquerading as ocular inflammation. METHODS: Case report. RESULTS: A 63-year-old woman with ocular history significant for cataract extraction with intraocular lens placement and retinal detachment repaired through pars plana vitrectomy and scleral buckle presents with anterior chamber inflammation and debris in the left eye. Uveitis workup was negative for any associated systemic disease. Anterior chamber washout and biopsy were nondiagnostic. At postoperative Month 1, she had recurrent anterior chamber debris and new debris noted in the vitreous cavity. A pars plana vitrectomy was performed, and during intraoperative scleral depression, copious strands of whitish material were expressed into the vitreous cavity. The scleral buckle was removed with additional whitish material noted within the encapsulated area. Papanicolaou stain of the material demonstrated a mixture of epithelial cells, histiocytes, lymphocytes, plasma cells, and neutrophils consistent with an epithelial cyst. CONCLUSION: Epithelial inclusion cysts are a rare complication of scleral buckle placement. These cysts are lined by a nonkeratinized, stratified squamous epithelium with or without goblet cells and most commonly occur after ocular trauma, inflammation, or surgical procedures. To the best of our knowledge, this is the first reported case of erosion of an epithelial inclusion cyst into the vitreous cavity.

Outcomes in Retinal Vein Occlusions Presenting with Poor Visual Acuity Treated with Anti-Vascular Endothelial Growth Factor Therapy: Prognosis and Predictive Factors.

PURPOSE: To present visual acuity and OCT outcomes in patients with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (VEGF) agents demonstrating poor initial visual acuity. We aimed to identify relevant factors that may portend differential outcomes in this important patient population. DESIGN: Retrospective chart review. PARTICIPANTS: Fifty-two patients with recent RVO treated with anti-VEGF therapy and demonstrating habitual corrected visual acuity of worse than 20/320 before any ocular therapy, with at least 6 months of follow-up. METHODS: Visual acuity, spectral-domain (SD) OCT findings, injection details, and the development of neovascular sequelae or need for adjunct therapies were recorded for consecutive visits after meeting vision criteria (maximum of 16 visits). In the central retinal vein occlusion (CRVO) cohort, univariate and multivariate analyses were performed to identify factors predictive of outcomes, and the incidence of sequelae was studied with survival analysis. MAIN OUTCOME MEASURES: Change in approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at 6 and 12 months. RESULTS: The CRVO patients (n = 39) gained a median of 20 letters relative to baseline at both 6 and 12 months and showed a change in central subfield thickness (CST) of -504.1 µm and -552.3 µm, respectively. Branch RVO and hemiretinal vein occlusion patients (n = 13) gained a median of +45 and +57.5 letters at 6 and 12 months, respectively, and showed reductions of 299.6 µm and 355.2 µm of CST on SD OCT. For CRVO patients, more time from symptom onset to first injection predicted less optimistic letter gains in unadjusted and adjusted models (P < 0.0001 for all measures). A delay from symptom onset to first injection of 30 days or more predicted higher incidence of both neovascular (hazard ratio, 11.036; 95% confidence interval [CI], 1.807-67.393) and total (hazard ratio, 11.425, 95% CI, 1.940-67.300) events. CONCLUSIONS: Patients with RVO demonstrating poor initial visual acuity showed visual and anatomic benefit with anti-VEGF therapy, most often observed shortly after initiation of treatment. In CRVO patients, even minor delays between symptom onset and first injection led to less optimistic vision gains and were associated with higher incidence of negative sequelae.

Loss of Peak Vision in Retinal Vein Occlusion Patients Treated for Macular Edema.

PURPOSE: To evaluate long-term visual and anatomic outcomes in patients with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (VEGF) agents. DESIGN: Prospective, interventional case series. PARTICIPANTS: Patients with central RVO (CRVO) or branch RVO (BRVO). METHODS: Number of anti-VEGF injections and improvement from baseline best-corrected visual acuity (BCVA) and central subfield thickness (CST) were prospectively recorded in 40 eyes of 39 CRVO patients and 50 eyes of 47 BRVO patients. RESULTS: Mean follow-up was 58 months for BRVO and 78 months for CRVO. Within 6 months of last follow-up, 58% of BRVO patients and 75% of CRVO patients required anti-VEGF injections to control edema. Analysis of the course of each patient over time showed that for BRVO patients, BCVA letter score increased by a mean of 24, from baseline of 52 (20/100) to peak of 76 (20/32), and subsequently decreased by 13, to 63 (20/50), at final visit; and for CRVO patients, BCVA letter score increased by a mean of 26, from baseline of 48 (20/100) to peak of 74 (20/32), and subsequently decreased by 18, to 56 (20/80), at last follow-up. Loss from peak BCVA occurred primarily owing to persistent/recurrent edema and related foveal damage. CONCLUSIONS: Patients with RVO showed large improvements in BCVA after initiation of anti-VEGF injections, but in many patients some visual gains were lost over time owing to bouts of recurrent edema. Sustained suppression of VEGF may help to provide optimal outcomes in RVO and reduce treatment burden.

Evolution of Choroidal Neovascularization due to Presumed Ocular Histoplasmosis Syndrome on Multimodal Imaging including Optical Coherence Tomography Angiography.

A 37-year-old Caucasian woman presented with acute decrease in central vision in her right eye and was found to have subfoveal choroidal neovascularization (CNV) due to presumed ocular histoplasmosis syndrome (POHS). Her visual acuity improved from 20/70 to 20/20 at her 6-month follow-up, after 3 consecutive monthly intravitreal bevacizumab injections were initiated at her first visit. Although no CNV activity was seen on fluorescein angiography (FA) or spectral-domain optical coherence tomography (SD-OCT) at her 2-month, 4-month, and 6-month follow-up visits, persistent flow in the CNV lesion was detected on optical coherence tomography angiography (OCTA). OCTA shows persistent vascular flow as well as changes in vascular flow in CNV lesions associated with POHS, indicating the continued presence of patent vessels and changes in these CNV lesions, even when traditional imaging of the lesion with OCT and FA indicates stability of the lesion with no disease activity. Additional cases with longitudinal follow-up are needed to assess how OCTA should be incorporated into clinical practice.

Congenital Retinal Macrovessel and the Association of Retinal Venous Malformations With Venous Malformations of the Brain.

Importance: Congenital retinal macrovessel (CRM) is a rarely reported venous malformation of the retina that is associated with venous anomalies of the brain. Objective: To study the multimodal imaging findings of a series of eyes with congenital retinal macrovessel and describe the systemic associations. Design, Setting, and Participants: In this cross-sectional multicenter study, medical records were retrospectively reviewed from 7 different retina clinics worldwide over a 10-year period (2007-2017). Patients with CRM, defined as an abnormal, large, macular vessel with a vascular distribution above and below the horizontal raphe, were identified. Data were analyzed from December 2016 to August 2017. Main Outcomes and Measures: Clinical information and multimodal retinal imaging findings were collected and studied. Pertinent systemic information, including brain magnetic resonance imaging findings, was also noted if available. Results: Of the 49 included patients, 32 (65%) were female, and the mean (SD) age at onset was 44.0 (20.9) years. A total of 49 eyes from 49 patients were studied. Macrovessel was unilateral in all patients. Color fundus photography illustrated a large aberrant dilated and tortuous retinal vein in all patients. Early-phase frames of fluorescein angiography further confirmed the venous nature of the macrovessel in 40 of 40 eyes. Optical coherence tomography angiography, available in 17 eyes (35%), displayed microvascular capillary abnormalities around the CRM, which were more evident in the deep capillary plexus. Of the 49 patients with CRM, 39 (80%) did not illustrate any evidence of ophthalmic complications. Ten patients (20%) presented with retinal complications, typically an incidental association with CRM. Twelve patients (24%) were noted to have venous malformations of the brain with associated magnetic resonance imaging. Of these, location of the venous anomaly in the brain was ipsilateral to the CRM in 10 patients (83%) and contralateral in 2 patients (17%), mainly located in the frontal lobe in 9 patients (75%). Conclusions and Relevance: Our study has identified an association between macrovessels in the retina and venous anomalies of the brain (24% compared with 0.2% to 6.0% in the normal population). Thus, we recommend new guidelines for the systemic workup of patients with CRM to include brain magnetic resonance imaging with contrast. These lesions may be more accurately referred to as retinal venous malformations, which may raise awareness regarding potential cerebral associations.

Shortest Distance From Fovea to Subfoveal Hemorrhage Border Is Important in Patients With Neovascular Age-related Macular Degeneration.

PURPOSE: To identify factors influencing visual outcome in patients with neovascular age-related macular degeneration (NVAMD) and subfoveal hemorrhage (SFH) treated with anti-vascular endothelial growth factor (VEGF) agents. DESIGN: Retrospective case series. METHODS: Anti-VEGF-treated eyes with SFH > 1 disc area (DA) were identified (n = 16) and changes in visual acuity (VA) and central subfield thickness (CST) from baseline to last follow-up, along with SFH area, thickness, minimum distance from fovea to SFH border, and time to resolution, were determined. RESULTS: At baseline, mean (± standard error of the mean) size and thickness of SFH were 14.9 ± 2.8 DA and 386.6 ± 46.9 µm, and mean Snellen VA and CST were 20/250 and 591.7 ± 57.0 µm. Median follow-up was 47.6 months. While more than 50% of patients had VA ≤ 20/200 at baseline and all time points through week 48, the percentage of patients with VA ≥ 20/50 increased to 30%-40% at months 6 and 12 and remained stable through month 48. Spearman rank correlation demonstrated 2 independent variables that correlated with good visual outcome, smaller area of SFH at baseline (r = -0.630; P = .009), and high frequency of anti-VEGF injections (r = 0.646; P = .007). In exceptional patients with good visual outcome despite large baseline SFH, shortest distance between the fovea and hemorrhage border significantly correlated with baseline VA (r = -0.503, P = .047) and final VA (r = -0.575, P = .02). CONCLUSIONS: Patients with NVAMD and thick SFH, but short distance between fovea and uninvolved retina, can have good visual outcomes when given frequent anti-VEGF injections.

Histopathological Insights Into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration.

IMPORTANCE: Age-related macular degeneration (AMD) is a multifactorial disease with genetic and environmental factors contributing to risk. Histopathologic changes underlying AMD are not fully understood, particularly the relationship between choriocapillaris (CC) dysfunction and phenotypic variability of this disease. OBJECTIVE: To examine histopathologic changes in the CC of eyes with clinically documented AMD. DESIGN, SETTING, AND PARTICIPANTS: The study was designed in 2011. Tissues were collected post mortem (2012-2016), and histopathological images were obtained from participants enrolled in AMD studies since 1988. Clinical records and images were collected from participants as standard protocol. Eyes without AMD (n = 4) and eyes with early (n = 9), intermediate (n = 5), and advanced stages of AMD (geographic atrophy, n = 5; neovascular disease, n = 13) were evaluated. Choroidal vasculature was labeled using Ulex europaeus agglutinin lectin and examined using confocal microscopy. MAIN OUTCOMES AND MEASURES: A standardized classification system was applied to determine AMD stage. Ocular records and images were reviewed and histopathologic analyses performed. Viability of the choroidal vasculature was analyzed for each AMD stage. RESULTS: All participants were white. Fourteen were male, and 16 were female. The mean age was 90.5 years among AMD patients and 88.5 years among control participants. Submacular CC dropout without retinal pigment eipthelial (RPE) loss was observed in all cases with early stages of AMD. Higher vascular area loss for each AMD stage was observed compared with control participants: 20.5% in early AMD (95% CI, 11.2%-40.2%; P < .001), 12.5% in intermediate AMD (95% CI, 2.9%-21.4%; P = .01), 39.0% loss in GA (95% CI, 32.1%-45.4%; P < .001), and 38.2% loss in neovascular disease where RPE remained intact (95% CI, 27.7%-47.9%; P < .001). Hypercellular, apparent neovascular buds were adjacent to areas of CC loss in 22.2% of eyes with early AMD and 40% of eyes with intermediate AMD. CONCLUSIONS AND RELEVANCE: Retinal pigment epithelial atrophy preceded CC loss in geographic atrophy, but CC loss occurred in the absence of RPE atrophy in 2 of 9 eyes with early-stage AMD. Given the cross-sectional nature of this study and the small number of eyes evaluated, definitive conclusions regarding this progression cannot be determined with certainty. We speculate that neovascular buds may be a precursor to neovascular disease. Hypoxic RPE resulting from reduced blood supply might upregulate production of vascular endothelial growth factor, providing the stimulus for neovascular disease.

Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial.

PURPOSE: The Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial measured aqueous pro-permeability factors (PPFs) in diabetic macular edema (DME) patients before and after injection of dexamethasone implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated changes in levels with changes in excess foveal thickness (EFT) to identify potential PPFs contributing to DME. DESIGN: Prospective, randomized crossover clinical trial. METHODS: Twenty DME patients randomized to dexamethasone implant or VEGF-neutralizing protein had aqueous taps and spectral-domain optical coherence tomography (SDOCT) at baseline and every 4 weeks for 28 weeks. Aqueous levels of 55 vasoactive proteins were measured with protein array. Crossover at week 16 provided changes in protein levels after each intervention in all 20 patients. RESULTS: After dexamethasone implant there was significant correlation between changes in levels of 13 vasoactive proteins with changes in EFT, including 3 known PPFs: angiopoietin-2 (r = 0.40, P = .001), hepatocyte growth factor (HGF; r = 0.31, P = .02), and endocrine gland-VEGF (EG-VEGF, r = 0.43, P < .001). Reduction of prolactin, insulin-like growth factor binding protein-3, and matrix metalloproteinase-9 correlated with edema reduction after injection of a VEGF-neutralizing protein as well as dexamethasone implant, suggesting their modulation is likely secondary to changes in edema rather than causative. CONCLUSIONS: Correlation of edema reduction with reduction in the PPFs angiopoietin-2, HGF, and EG-VEGF provides potential insight into the multifactorial molecular mechanism by which dexamethasone implants reduce edema and suggest that additional study is needed to investigate the contributions of these 3 factors to chronic DME.

DEVELOPMENT OF CHRONIC SUBRETINAL FLUID IN KEARNS-SAYRE SYNDROME.

BACKGROUND/PURPOSE: To report a novel ophthalmic finding of the development of chronic subretinal fluid in a patient with Kearns-Sayre syndrome. METHODS: An observational case report with funduscopic, angiographic, neurophysiologic, and optical coherence tomographic correlation. RESULTS: An 11-year-old male with bilateral hearing loss, cerebellar dysfunction, short stature, low weight, ptosis, external ophthalmoplegia, and pigmentary retinopathy of both eyes developed chronic subretinal fluid below the central macula. This fluid has remained for more than 1.5 years. Genetic testing revealed a heteroplasmic 7,797 base pair mitochondrial deletion (m. 7638-1543del7797). CONCLUSIONS: The authors report a novel physical finding of subfoveal fluid in a patient with Kearns-Sayre syndrome. The pathophysiologic etiology of this fluid and its localization to the subfoveal retina remains unclear. Patients with pigmentary retinopathy related to mitochondrial disorders should be monitored for the development of subretinal fluid, which can contribute to vision loss.

Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion.

PURPOSE: To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab. DESIGN: Secondary outcome measure in randomized double-masked controlled clinical trial. PARTICIPANTS: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). METHODS: Subjects were randomized to 0.5 or 2.0 mg ranibizumab every month for 6 months and then were re-randomized to pro re nata (PRN) groups receiving either ranibizumab plus scatter laser photocoagulation or ranibizumab alone for an additional 30 months. MAIN OUTCOME MEASURES: Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5 versus 2.0 mg ranibizumab, during monthly injections versus ranibizumab PRN, and in patients treated with ranibizumab PRN versus ranibizumab PRN plus laser. RESULTS: In RVO patients given monthly injections of 0.5 or 2.0 mg ranibizumab for 6 months, there was no significant difference in the percentage who showed reduction or increase in the area of RNP. However, regardless of dose, during the 6-month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared with subsequent periods of ranibizumab PRN treatment. After the 6-month period of monthly injections, BRVO patients, but not CRVO patients, randomized to ranibizumab PRN plus laser showed significantly less progression of RNP compared with patients treated with ranibizumab PRN. CONCLUSIONS: Regardless of dose (0.5 or 2.0 mg), monthly ranibizumab injections promote improvement and reduce progression of RNP compared with PRN injections. The addition of scatter photocoagulation to ranibizumab PRN may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO.

Interventions for central serous chorioretinopathy: a network meta-analysis.

BACKGROUND: Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. OBJECTIVES: To compare the relative effectiveness of interventions for central serous chorioretinopathy. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. SELECTION CRITERIA: Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model. MAIN RESULTS: We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked.The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC.Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) -0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted.Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD -0.10 logMAR, 95% CI -0.18 to -0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted.Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI -0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants).Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD -0.20 logMAR, 95% CI -0.30 to -0.11; 45 participants). There were no significant adverse effects noted.Other comparisons were largely inconclusive.We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified. AUTHORS' CONCLUSIONS: CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials.