Altered fatty acid distribution in lysosome-associated membrane protein-2 deficient mice.

Lysosome-associated membrane protein-2 (LAMP2) deficiency causes the human Danon disease and represents a lysosomal dysfunction because of its pivotal role in regulating autophagy and lysosome biogenesis. LAMP2-deficient mice exhibit a spectrum of phenotypes, including cardioskeletal myopathy, mental retardation, and retinopathy, similar to those observed in patients with Danon disease. Its pathology is thought to involve altered energy metabolism and lipid dysregulation; however, the lipidomic profiles of LAMP2-deficient animals have not been investigated. In this study, we investigated lipid alterations in LAMP2 KO mice tissues, including those of the liver, plasma, and retina, using liquid chromatography-mass spectrometry. Our results revealed significantly increased free fatty acid (FFA) levels and decreased in triglyceride (TG) levels in LAMP2 KO liver tissues at three and six months. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species significantly decreased in LAMP2 KO mice livers at six months. Similarly, plasma TG and PC/PE levels decreased in LAMP2 KO mice. In contrast, plasma FFA levels were significantly lower in LAMP2 KO mice. Retina FFA levels were elevated in LAMP2 KO mice, accompanied by a partial decrease in PC/PE at six months. In summary, FFA levels increased in several tissues but not in the LAMP2 KO mice plasma, suggesting the potential consumption of FFA as an energy source in the peripheral tissues. The depletion of TG and PC/PE accelerated with age, suggesting an underlying age-dependent energy crisis condition. Our findings underscore the dysregulated distribution of fatty acids in LAMP2-deficient animals and provide new mechanistic insights into the pathology of Danon disease.

A Recurrent Case of Full-Thickness Macular Hole After Successful Closure With Primary Vitrectomy and Epiretinal Proliferation Embedding.

Epiretinal proliferation (EP) is thought to be glial cell proliferation arising from the inner retina, seen in cases of lamellar or full-thickness macular holes (FTMH). Embedding EP within the macular hole is considered supportive for FTMH closure and functional recovery. We report a recurrent case of FTMH that was successfully closed after primary vitrectomy with the EP embedding technique. In the primary surgery, internal limiting membrane (ILM) peeling was avoided to reduce the potential risk of retinal nerve fiber layer damage associated with glaucoma. The FTMH was successfully closed, with complete recovery of macular layer structures. However, over one year later, the FTMH reopened, slightly dislocated from the position of the embedded EP scar. The reopened FTMH was closed again after the second surgery using the ILM inverted flap technique. This case indicates that macular hole closure with EP might not sufficiently support the tissue repair of FTMH as a new hole can form if tangential traction of the ILM remains.

Postoperative Proliferation Detection in Eyes Treated for Rhegmatogenous Retinal Detachment by WideField OCT Angiography.

Purpose: Proliferative retinal changes may occur postsurgery for rhegmatogenous retinal detachment (RRD), possibly preceding recurrent detachment. This study aims to establish the groundwork for an imaging system capable of discerning changes in retinal vessel tortuosity after RRD repair, analyzing widefield optical coherence tomography angiography (WF-OCTA) images. Methods: Eighty-eight eyes of 86 patients with RRD who underwent surgical procedures and had repeated imaging with clear widefield optical coherence tomography (WF-OCT) and WF-OCTA on different postoperative days were enrolled in this retrospective study. We compared WF-OCTA images over time to identify alterations in retinal vessel tortuosity and observed regional changes in retinal morphology. Results: After image processing, changes in retinal vessel tortuosity were detected in 66 quadrants. These changes, attributed to retinal traction from proliferative membranes, were observed in 56 quadrants, among which retinal thickness remained unchanged in seven sectors (12.5%) according to the WF-OCT map. In nine quadrants, changes in retinal vessel tortuosity were attributed to changes in subretinal fluid, aligning with observable variations in retinal thickness. Conclusions: Observation of vessel tortuosity changes using WF-OCTA can help detect early postoperative proliferative changes in eyes with RRD. Translational Relevance: Because WF-OCTA can detect minute vessel tortuosity changes, it can offer a noninvasive alternative for the detection of early postoperative proliferative changes.

Factors at the initial visit associated with poor visual outcomes in patients with acute retinal necrosis.

BACKGROUND/OBJECTIVE: Acute retinal necrosis (ARN) is a vision-threatening disease caused by herpesvirus infection. This study aimed to investigate the visual prognostic factors that could be determined at the initial visit. SUBJECTS AND METHODS: This retrospective study included 34 patients with ARN. Logistic regression analysis was employed to evaluate the associations between poor final visual outcomes and various factors, including poor initial visual acuity, presence of retinal detachment at the initial visit, posterior extension of necrotizing retinitis, and circumferential extension of necrotizing retinitis. Posterior extension was evaluated with three zonings, from the periphery (zone 3), mid-periphery (zone 2), and macula (zone 1). Circumferential extension was evaluated according to the degree of necrotizing retinitis lesions using ultra-wide fundus imaging. RESULTS: The mean logarithm of the minimum angle of resolution was 0.63 ± 0.68 at the initial visit and 0.83 ± 0.65 at 12 months after the initial visit. Seven patients had a retinal detachment. The distribution of posterior extension at the initial visit was 5 in zone 1, 20 in zone 2, and 9 in zone 3. The average of necrotizing retinitis lesion angle was 249 ± 115°. The logistic regression analysis revealed that participants with wide angles of necrotizing retinitis were associated with final poor vision, with an odds ratio of 1.28 per 30° increase (95%CI: 1.00-1.65, p = 0.03). CONCLUSIONS: Assessment of the widespread circumferential extension of white necrotizing retinal lesions at the initial visit is a crucial risk factor for the visual prognosis in ARN.

Intraocular kinetics of pathological ATP after photoreceptor damage in rhegmatogenous retinal detachment.

PURPOSE: Extracellular Adenosine triphosphate (ATP) released by dying cells may cause a secondary cell death in neighboring cells in retinal degeneration. We investigated intraocular ATP kinetics to gain mechanical insights into the pathology in rhegmatogenous retinal detachment (RRD). STUDY DESIGN: Retrospective clinical study. METHODS: Vitreous or subretinal fluids (SRF) were obtained from patients with RRD (n=75), macular hole (MH; n=20), and epiretinal membrane (ERM; n=35) during vitrectomy. ATP levels in those samples were measured by luciferase assay. RESULTS: Mean ATP levels in the vitreous from RRD patients were significantly higher compared to those from MH and ERM patients (2.3 and 0.3 nM, respectively. P<0.01). Mean ATP levels in the SRF from RRD (11.7 nM) were higher than those in the vitreous from RRD (P<0.01). Mean ATP levels in the vitreous with short durations (1-8 days) of RRD were higher compared to those with long durations (>8 days) (3.2 and 1.4 nM, respectively. P<0.05). Similarly, ATP in SRF with short durations were higher than those with long durations (23.8 and 3.6 nM, respectively. P<0.05). Furthermore, the concentrations of ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1), a major ATP degradative enzyme, in the vitreous from RRD were higher than those from MH/ERM (1.2 and 0.2 ng/ml, respectively. P<0.01). ENTPD1 expression was localized in the cytoplasm of CD11b-positive infiltrating cells in the vitreous and retinal cells. CONCLUSION: ATP increased in the vitreous and SRF in RRD and decreased over time with an upregulation of ENTPD1. The kinetics indicate the pathological mechanism of the excessive extracellular ATP after RRD.

Three-month outcomes of treatment with faricimab or aflibercept for neovascular age-related macular degeneration: a propensity score matching study in a Japanese population.

PURPOSE: This study aimed to compare the treatment outcomes of patients with neovascular age-related macular degeneration (nAMD) who initially received faricimab or aflibercept treatment using propensity score matching (PSM) to align patient backgrounds. METHODS: Patients with treatment-naïve nAMD who received either faricimab or aflibercept for three consecutive monthly injections as the loading phase were enrolled in this study. In the 1:1 PSM, sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and AMD subtypes in the pre-treatment state were selected as covariates. We examined the BCVA, CMT, CCT, and remaining fluid at 1-, 2-, and 3-month after the first injection. RESULTS: After PSM, 43 eyes were included in the faricimab and aflibercept group each. Both groups showed significant improvements in BCVA, CMT, and CCT at 1-, 2-, and 3-month after the initial injection compared with baseline. Meanwhile, no significant differences were observed between the two groups at any time point regarding BCVA, CMT, and CCT. At 1-month, 18.6% of patients in the faricimab group and 41.9% in the aflibercept group demonstrated residual subretinal fluid or intraretinal fluid, with a significant difference between the groups (P = 0.03). CONCLUSION: The BCVA improved after three loading injections of both faricimab and aflibercept. Faricimab may provide a favorable early treatment response in reducing subretinal fluid in a Japanese cohort.

The factors associated with retinal pigment epithelium tear development in the early phase after treatment initiation for age-related macular degeneration.

PURPOSE: This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED). METHODS: Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3 months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3 months of starting anti-VEGF therapy was examined. RESULTS: This study included 244 eyes (230 patients; mean age 75.0 years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3 months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100 µm, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07-2.12, p = 0.019), PED area (every 10 mm2, OR: 3.02, CI: 1.22-7.46, p = 0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12-850.59, p = 0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p = 0.01, χ-square test). CONCLUSIONS: Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs.

Wide-Field Choroidal Thickness Analysis after Half-Fluence Photodynamic Therapy Combined with Intravitreal Aflibercept Injection in Pachychoroid Neovasculopathy.

Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Methods: Seventeen eyes with PNV that underwent half-fluence PDT with an adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9-18 mm from the fovea. The <9 and 9-18 mm subfields were divided into four quadrants. Results: Choroidal thickness in each subfield decreased significantly after half-fluence PDT (p < 0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9 mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. Conclusions: Half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

Clinical Characteristics of Eyes with Neovascular Age-Related Macular Degeneration and Retinal Pigment Epithelium Tears.

BACKGROUND: Although anti-vascular endothelial growth factor (anti-VEGF) therapy is the first choice of treatment for eyes with neovascular age-related macular degeneration (AMD), it sometimes results in retinal pigment epithelium (RPE) tears. This study presents the detailed clinical characteristics of RPE tears to help predict their occurrence before anti-VEGF therapy initiation. METHODS: This study retrospectively analyzed neovascular age-related macular degeneration (nAMD) patients who visited the Kyushu University Hospital and started anti-VEGF therapy between April 2013 and June 2020. Using medical records, we collected the clinical data of patients with RPE tears, including age, sex, best-corrected visual acuity (BCVA), number of anti-VEGF drug injections and the type and size of pigment epithelial detachment (PED). RESULTS: RPE tears occurred in 16 (1.50%) eyes of 16 patients in all 1068 nAMD eyes of 987 patients. The mean age of these patients with RPE tear was 81.7 ± 8.7 years. Fifteen eyes had typical AMD and one eye had polypoidal choroidal vasculopathy. The mean number of anti-VEGF drug injections before RPE tears was 5.0 ± 5.1. All patients experienced PED before the RPE tear (hemorrhagic, 4 eyes; serous vascular, 2 eyes; fibrovascular, 10 eyes). The average PED height and area were 615.7 ± 175.3 µm and 21.0 ± 7.2 mm2, respectively. The sub-RPE cleft was observed in 10 eyes. The logMAR BCVA immediately after the RPE tear (0.73 ± 0.40) at 6 months (0.86 ± 0.51) and 12 months (0.84 ± 0.43) after the RPE tear were significantly worse than that before the RPE tear (0.58 ± 0.31; p < 0.05). The BCVA of patients with RPE tears that spread to the fovea was poorer than that of patients without RPE tears. CONCLUSIONS: In patients with nAMD, RPE tears tended to occur in typical AMD eyes with high or large PEDs, and sub-RPE clefts. The visual prognosis depended on whether the RPE tear included the fovea.

Differences in Central and Peripheral Choroidal Thickness among the Subtypes of Age-Related Macular Degeneration in an Asian Population.

Age-related macular degeneration (AMD) causes visual impairment in individuals who are >50 years of age. However, no study has investigated AMD when using ultra-wide-field swept-source optical coherence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thicknesses using UWF SS-OCT, and to compare these across the AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare choroidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9-18 mm from the fovea. PNV patients were significantly younger than those with tAMD (p = 0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (p < 0.01), and choroidal thickness significantly correlated with age and axial length in all subfields (p < 0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.05). In addition, the ratio of the posterior <9 mm to a peripheral 9-18 mm choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.

Characteristics of retinal pigment epithelium elevations preceding exudative age-related macular degeneration in Japanese.

INTRODUCTION: Drusen and pigmentary abnormality are found as the hallmark to predict progression of age-related macular degeneration (AMD). In Asian populations, exudative AMD often appears in the absence of drusen but are rather accompanied by pigmentary abnormality. Recently, shallow irregular retinal-pigment-epithelium (RPE) elevations (SIRE) has been shown as a sign of subclinical non-exudative macular neovascularization. In this study, we aimed to investigate the characteristics of optical coherence tomography (OCT) findings including SIRE before the appearance of exudative AMD. METHODS: We retrospective reviewed 32 cases of exudative AMD that occurred in the fellow eye within the 5-years-observation period. Color fundus photography, OCT, and fluorescein/indocyanine green angiography at the beginning of observation and at the time when exudative AMD appeared were examined to diagnose SIRE and the subtype of exudative AMD. RESULTS: Exudative AMD were found in 19 eyes with large drusen and 13 eyes without large drusen. Mean sub-foveal choroidal thickness without large drusen were significantly thicker than those with large drusen (336 ± 109 and 220 ± 96 µm, respectively; mean± SD). Six eyes with pachychoroid neovasculopathy, 4 eyes with Type 1 macular neovascularization, and 3 eyes with PCV had occurred in the fellow eye without large drusen. Among those, 6 eyes had been accompanied by SIRE with a greatest transverse linear dimension of 1 mm or more at the beginning of observation-period. Besides, small RPE elevations with a longest diameter of less than 1 mm had been observed in other 5 eyes. Three cases of polypoidal choroidal vasculopathy had originated from small RPE elevations. Moreover, pachyvessels, choriocapillaris thinning, or choroidal hyperpermeability were observed with SIRE or small RPE elevation. CONCLUSIONS: There is a non-drusen type of exudative AMD that originates from small RPE elevations as well as SIRE.

A Case of Bullous Central Serous Chorioretinopathy Treated with Surgical Removal of Submacular Fibrin and Subsequent Photodynamic Therapy under Silicone Oil.

Bullous retinal detachment is a rare complication in the chronic phase of central serous chorioretinopathy (CSC). Only a small subset of eyes with chronic CSC develops into the bullous variant of CSC (bCSC). In patients with bCSC, the elevated concentration of fibrin in the subretinal space leads to persistent retinal detachment and eventually, severe vision loss. We experienced a case of unilateral bCSC with a massive accumulation of subretinal fibrin. Multiple leakage points and dilated choroidal veins were also observed. The patient underwent surgical removal of subretinal fibrin and silicone oil injection followed by photodynamic therapy (PDT). After this treatment, the retina was successfully reattached, and the affected eye was free from recurrent exudative changes for more than 18 months. Massive subretinal fibrin could be surgically removed to prevent the formation of subretinal fibrosis and retinal fold, and PDT under silicone oil can control the underlying exudative changes in bCSC.

Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa.

Retinitis pigmentosa (RP) is an intractable inherited disease that primarily affects the rods through gene mutations followed by secondary cone degeneration. This cone-related dysfunction can lead to impairment of daily life activities, and ultimately blindness in patients with RP. Paradoxically, microglial neuroinflammation contributes to both protection against and progression of RP, but it is unclear which population(s) - tissue-resident microglia and/or peripheral monocyte-derived macrophages (mφ) - are implicated in the progression of the disease. Here we show that circulating blood inflammatory monocytes (IMo) are key effector cells that mediate cone cell death in RP. Attenuation of IMo and peripherally engrafted mφ by Ccl2 deficiency or immune modulation via intravenous nano-particle treatment suppressed cone cell death in rd10 mice, an animal model of RP. In contrast, the depletion of resident microglia by a colony-stimulating factor 1 receptor inhibitor exacerbated cone cell death in the same model. In human patients with RP, IMo was increased and correlated with disease progression. These results suggest that peripheral IMo is a potential target to delay cone cell death and prevent blindness in RP.

Increased vitreous levels of B cell activation factor (BAFF) and soluble interleukin-6 receptor in patients with macular edema due to uveitis related to Behçet's disease and sarcoidosis.

PURPOSE: Uveitis accounts for 10-15% of all cases of blindness in the developed world. Uveitic macular edema (UME) is a primary cause of permanent visual impairment in patients with uveitis. Because proinflammatory mediators elicit inflammation and lead to UME, we determined the profiles of proinflammatory mediators associated with complications, such as ME, in the vitreous humor of patients with panuveitis related to Behçet's disease (BD) and sarcoidosis. METHODS: In this retrospective study, we enrolled 21 patients with uveitis, including 6 with BD and 15 with sarcoidosis, and 15 patients with idiopathic epiretinal membrane (iERM) at the Department of Ophthalmology, Kyushu University Hospital, between January 2008 and April 2016. Vitreous concentrations of 32 proinflammatory mediators, including cytokines and soluble receptors of tumor necrosis factor (TNF) and interleukin (IL)-6 families, were assessed using a bead-based multiplex assay and their association with clinical data was examined. RESULTS: The levels of proinflammatory mediators, including a proliferation-inducing ligand (APRIL), B cell activating factor belonging to the TNF family (BAFF), soluble cluster of differentiation 30 (sCD30), soluble TNF receptor-1 (sTNFR1), sTNFR2, TNF-α, IL-6, and soluble IL-6 receptor-α (sIL-6Rα), were significantly higher in patients with uveitis. With regard to clinical parameters in patients with uveitis, vitreous levels of BAFF and sIL-6Rα were prominently elevated in patients with UME compared to in those without UME (P < 0.01, respectively). CONCLUSIONS: Our results suggest that elevated vitreous levels of BAFF and sIL-6Rα are associated with the pathogenesis of UME in patients with panuveitis related to BD and sarcoidosis.

TNFRSF10A downregulation induces retinal pigment epithelium degeneration during the pathogenesis of age-related macular degeneration and central serous chorioretinopathy.

Age-related macular degeneration (AMD) and central serous chorioretinopathy (CSC) are common diseases that can cause vision loss in older and younger populations. These diseases share pathophysiological conditions derived from retinal pigment epithelium (RPE) dysfunction. Tumor necrosis factor receptor superfamily 10A (TNFRSF10A)-LOC389641 with the same lead single-nucleotide polymorphism (SNP) (rs13278062) is the only overlapped susceptibility locus found in both AMD and CSC through genome-wide association studies. This lead SNP has been reported to alter the transcriptional activity of TNFRSF10A. This study aimed to elucidate the function of TNFRSF10A in RPE degeneration using human primary RPE cells and Tnfrsf10 knockout (Tnfrsf10-/-) mice. TNFRSF10A was found to be localized in human RPE. In vitro assays revealed that a T allele of rs13278062, the risk allele for AMD and CSC, downregulated TNFRSF10A transcription in RPE, leading to decreased cell viability and increased apoptosis through protein kinase C-α (PKCA) downregulation. Treatment with phorbol 12-myristate 13-acetate, a PKC activator, rescued the cell viability. Morphological RPE abnormality was found in the retina of Tnfrsf10-/- mice. Our data suggest that downregulation of TNFRSF10A expression inactivates PKCA signaling and causes cellular vulnerability of the RPE, which may contribute to the pathogenesis of AMD and CSC.

One-year efficacy of "rescue photodynamic therapy" for patients with typical age-related macular degeneration, polypoidal choroidal vasculopathy, and pachychoroid neovasculopathy refractory to anti-vascular endothelial growth factor therapy.

PURPOSE: This study aimed to evaluate the one-year outcomes of photodynamic therapy (PDT) as a rescue treatment for age-related macular degeneration (AMD) refractory to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Patients with AMD refractory to anti-VEGF therapy, treated with "rescue-PDT" were retrospectively investigated. The time of PDT was defined as the baseline value. Baseline characteristics including sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), and foveal choroidal thickness (FCT) were examined. The changes in BCVA, CMT, and recurrence were also assessed at the 1-year follow-up. The logMAR VA change of 0.3 or more was defined as "improved" or "declined." RESULTS: Twenty-three consecutive eyes (typical AMD: 10 eyes, polypoidal choroidal vasculopathy: 10 eyes, and pachychoroid neovasculopathy: 3 eyes), which underwent "rescue-PDT," were analyzed in this study. The BCVA was improved in three patients and maintained in 20 patients at 12 months after PDT (mean BCVA change: 0.11 ± 0.19). The CMT improved in 19 patients (82.6%), and the mean CMT changed from 318.5 ± 93.7 µm to 225.9 ± 51.6 µm (p < 0.01) 12 months after PDT. "Retreatment" of anti-VEGF drug injections was considered if the retinal fluid or retinal hemorrhage recurred after PDT. The baseline FCT of the "retreatment group (15 eyes)" was significantly lower than that of the "no retreatment group (8 eyes)" (206.3 ± 50.7 µm vs 293.9 ± 85.7 µm: p = 0.033). CONCLUSIONS: PDT could be an effective treatment option for anti-VEGF refractory AMD to maintain visual acuity and control retinal fluid for up to 12 months.

Spatial pattern of retinal pigment epithelium tear development and progression after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration.

PURPOSE: To demonstrate the spatial pattern of retinal pigment epithelium (RPE) tear development and progression following anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD). METHODS: We retrospectively reviewed six eyes with nAMD that showed RPE tears after administration of intravitreal anti-VEGF agents and were followed up for 12 months. The patterns of RPE tear development and progression were evaluated by analyzing positional relationships among the locations of the choroidal neovascularization membrane (CNVM) and pigment epithelial detachment (PED) area at baseline and the tear area via spectral-domain optical coherence tomography (SD-OCT), color photography, fluorescein angiography, and fundus autofluorescence images. RESULTS: Pre-tear OCT images revealed fibrovascular PED in all eyes, one of which showed complications of hemorrhagic PED after treatment. In five eyes, RPE tears developed at the PED edge located on the opposite side of the CNVM. In the eye showing hemorrhagic PED, the RPE tear developed along the wide area of the PED edge. The torn RPE monolayer contracted toward the side of the CNVM in all eyes and RPE loss involved the fovea in five eyes that showed significantly worse visual acuity (VA) after 12 months in comparison with the baseline value before the tear (logMAR VA; 0.3 vs. 1.29; P < 0.02). CONCLUSION: The location of CNVM in PED determines the spatial pattern of RPE tear development and progression and helps to predict the visual outcome after RPE tears.

Drainage Retinotomy Confers Risk of Epiretinal Membrane Formation After Vitrectomy for Rhegmatogenous Retinal Detachment Repair.

PURPOSE: To describe the factors associated with epiretinal membrane (ERM) formation in eyes treated with pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). DESIGN: Nationwide, multicenter, clinical cohort study based on registry data. METHODS: We reviewed 2239 cases treated with PPV for RRD repair registered in the Japan-Retinal Detachment Registry between February 2016 and March 2017. Associations of 13 baseline characteristics and 8 surgical procedures with ERM formation were evaluated using univariate analysis. We conducted a propensity score-matched analysis for the significantly associated clinical factor(s). The primary outcome measure was ERM formation after 6 months of vitrectomy. RESULTS: ERM had developed in 104 cases (4.6%) by 6 months. We found that drainage retinotomy was significantly associated with ERM after multiple testing correction (odds ratio [OR] 2.22 [95% confidence interval {CI} 1.50-3.31]; P < .001). In the propensity score-matched analysis (n = 492 in each group), we confirmed a significant difference in the incidence of ERM after 6 months of vitrectomy (8.3% and 2.6% in cases with and without drainage retinotomy, respectively; OR 3.35 [95% CI 1.77-6.33]; P < .001). CONCLUSIONS: Eyes treated with PPV combined with drainage retinotomy are more likely to develop ERM postoperatively.