IMPACT OF MACULAR INTRARETINAL HEMORRHAGE AND MACULAR HOLE ON THE VISUAL PROGNOSIS OF SUBMACULAR HEMORRHAGE DUE TO RETINAL ARTERIAL MACROANEURYSM RUPTURE.

PURPOSE: To compare the effects of macular intraretinal hemorrhage (IRH) and macular hole (MH) on best-corrected visual acuity (BCVA) after displacement of submacular hemorrhage (SMH) due to retinal arterial macroaneurysm (RAM) rupture. METHODS: This multicenter retrospective study included 48 eyes with SMH due to RAM rupture. Cases underwent vitrectomy to displace SMH and were followed up for 6 months. We classified cases according to the presence of IRH and MH and compared the postoperative BCVA among the groups. RESULTS: We classified the eyes into IRH(+)MH(+) group (10 eyes), IRH(+)MH(-) group (23 eyes), and IRH(-)MH(-) group (15 eyes). The postoperative BCVA was significantly worse in the IRH(+)MH(+) and IRH(+)MH(-) groups than in the IRH(-)MH(-) group (0.91 ± 0.41 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/163, 0.87 ± 0.45, 20/148, and 0.18 ± 0.21, 20/30, respectively; P < 0.001). The postoperative central retinal thickness was significantly lower in the IRH(+) group (IRH(+)MH(+) and IRH(+)MH(-) groups combined) than in the IRH(-) group (IRH(-)MH(-) group) (121.4 ± 70.1 µ m and 174.3 ± 32.9 µ m, respectively, P = 0.008). The postoperative external limiting membrane and ellipsoid zone continuities were significantly discontinuous in the IRH(+) group ( P < 0.001, P = 0.001, respectively). The multiple linear regression analysis showed that both IRH(+)MH(+) and IRH(+)MH(-) were associated with the postoperative BCVA (regression coefficient, 0.799 and 0.711, respectively; P < 0.001 for both). CONCLUSION: Both IRH and MH were poor prognostic indicators in cases with SMH due to RAM rupture.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Transscleral drainage to treat peripheral exudative hemorrhagic chorioretinopathy caused by retinal pigment epithelial hemorrhage.

Purpose: To report a case of peripheral exudative hemorrhagic chorioretinopathy with hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage treated with transscleral subretinal fluid drainage. Observations: The patient was a 70-year-old man with a 15-year history of diabetic retinopathy and age-related macular degeneration. During follow-up, he developed a sudden decrease in visual acuity in the left eye. Corrected visual acuity was 20/32 in the right eye and 20/800 in the left eye, and hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage were observed in the left eye. Pars plana vitrectomy and transscleral drainage of the subretinal hemorrhage and subretinal pigment epithelial hemorrhage were performed. We initially attempted to displace the subretinal pigment epithelial hemorrhage, but the subretinal hemorrhage was also displaced via a retinal pigment epithelial tear located in the temporal macula. The retina was completely reattached, although visual acuity in the left eye remained at 20/400. Conclusions and Importance: This report describes a surgical technique for hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage due to peripheral exudative hemorrhagic chorioretinopathy. We believe that transscleral subretinal fluid drainage without intentional retinal tear is a useful and safe method for patients with extensive hemorrhagic retinal detachment.

Intraocular lens extraction using the cartridge pull-through technique.

Current intraocular lens (IOL) explantation techniques are limited to cutting the optic and removing the pieces through a small incision or folding single-piece acrylic IOLs using a 2-handed technique. Poor execution of IOL explantation can result in injury to intraocular structures, including the corneal endothelium and iris. The minimally invasive cartridge pull-through technique uses a cartridge for IOL implantation and new forceps optimized for secure grasping of the IOL for removal. This method involved less manipulation in the anterior chamber, thereby reducing the risks for complications such as corneal and iris injuries. A dropped IOL lying on the retinal surface can be extracted directly without lifting it onto the iris first. The cartridge pull-through technique offers a more streamlined and potentially safer approach for IOL explantation.

Inverted Internal Limiting Membrane Flap versus Internal Limiting Membrane Peeling for Macular Hole Retinal Detachment in High Myopia.

PURPOSE: To compare surgical outcomes between the inverted internal limiting membrane (ILM) flap technique and ILM peeling for macular hole retinal detachment (MHRD) in eyes with high myopia. DESIGN: Multicenter cohort study. PARTICIPANTS: We retrospectively reviewed medical records of consecutive patients treated between June 2008 and September 2018 at 7 hospitals and included 100 eyes with MHRD associated with high myopia in our study. All eyes underwent vitrectomy with the inverted ILM flap technique (57 eyes) or ILM peeling (43 eyes) and were followed up for more than 6 months. METHODS: We estimated odds ratios and their 95% confidence intervals (CIs) for macular hole (MH) closure using multivariate logistic regression analysis. We also examined factors associated with the postoperative best-corrected visual acuity (BCVA) at the final visit using multiple linear regression analysis. MAIN OUTCOME MEASURES: Macular hole closure and postoperative BCVA at the final visit. RESULTS: The MH closure rate was significantly higher in the inverted ILM flap group (80.7%) than in the ILM peeling group (37.2%; P < 0.001). Moreover, postoperative BCVA at the final visit was significantly better in the former group (0.88 ± 0.48 vs. 0.99 ± 0.48; P = 0.03). The retinal attachment rate (ILM flap, 91.2%; ILM peeling, 79.5%; P = 0.229) and recovery rates for the external limiting membrane and ellipsoid zone line (ILM flap, 10.9%; ILM peeling, 0%; P = 0.12) showed no significant intergroup differences. After adjustment for age, axis, tamponade substance, and dye for ILM staining, the inverted ILM flap technique was associated strongly and positively with MH closure (odds ratio, 7.14; 95% CI, 2.72-18.7; P = 0.001). Moreover, the inverted ILM flap technique and preoperative BCVA were associated significantly and positively with the postoperative BCVA at the final visit. CONCLUSIONS: Our findings suggest that the MH closure rate and postoperative visual outcome for eyes with high myopia-associated MHRD are better with the inverted ILM flap technique than with ILM peeling. Thus, vitrectomy with the inverted ILM flap technique should be considered as the initial surgery for MHRD associated with high myopia.

A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Indocyanine green angiography in patients with human T cell-lymphotropic virus type 1 uveitis.

PURPOSE: To determine the indocyanine green (ICG) angiographic features and to evaluate the choroidal involvement of human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis. METHODS: We performed ICG angiography using scanning laser ophthalmoscopy in 54 eyes of 27 patients (8 men and 19 women) diagnosed with HTLV-1 uveitis. The patient's mean age was 51.5 years with a range of 24-65 years. RESULTS: The early phase of ICG angiography revealed ICG leakage from the choroidal vessels in the posterior pole, hyperfluorescent spots that which were not detected with fluorescein angiography, and small hypofluorescent lesions in the macula which most likely corresponded to microcirculatory disturbances in the choriocapillaris. CONCLUSIONS: We suggest that the ICG angiographic findings reflect choroidal lesions such as infiltration with leukocytes and edema. ICG angiography may provide useful information on choroidopathy in HTLV-1 uveitis.