Relationships between causative genes and epiretinal membrane formation in Japanese patients with retinitis pigmentosa.

PURPOSE: To investigate the relationships between macular complications and causative genes frequently found in Japanese patients with retinitis pigmentosa (RP). METHODS: In the retrospective and observational study, we analyzed the data of 75 patients with RP (EYS-RP: 42 patients; USH2A-RP: 19 patients; RHO-RP: 14 patients) who were followed-up at Kyushu University Hospital and whose causative genes had been identified. Macular complications including epiretinal membrane (ERM), macular edema (ME), and macular hole (MH) were evaluated using optical coherence tomography and fundus photography. Main outcome was the proportion of macular complications. RESULTS: The proportion of ERM was 35.7% in the EYS group, 10.5% in the USH2A group and 14.3% in the RHO group. The proportion of ME was 7.1% in the EYS group, 5.3% in the USH2A group and 14.3% in the RHO group, and that of MH was 2.4% in the EYS group, 5.3% in the USH2A group and 0% in the RHO group. In the EYS group, the proportion of ERM was relatively higher (p = 0.06), and the presence of EYS was significantly associated with a higher age- and sex-adjusted OR for ERM (OR = 5.67, 95% CI = 1.59-25.20). There was no significant difference in the proportion of MH or ME among causative genes. CONCLUSIONS: EYS causative gene may be associated with higher rate of ERM complication in RP.

Serous Retinal Detachment without Leakage on Fluorescein/Indocyanine Angiography in MEK Inhibitor-Associated Retinopathy.

The aim of this paper was to report the cases of 3 consecutive patients with mitogen-activated protein kinase kinase inhibitor (MEKi)-associated retinopathy with characteristic multiple serous retinal detachments (SRDs). A functional analysis of the retinal pigment epithelium was performed in 2 patients by electro-oculography (EOG). In all 3 patients, SRD lesions were observed in the posterior pole including the fovea of both eyes. Interestingly, neither obvious leakage in fluorescein/indocyanine angiography nor abnormal fundus autofluorescence was associated. SRDs and associated cystoid macular edema in one case rapidly resolved with the cessation of MEKi but recurred quickly after treatment resumption. In EOG tests, three of four eyes with multiple SRDs showed a marked decrease in the light-peak-to-dark-trough ratio (LP:DT ratio). The LP:DT ratio in EOG reflects the transepithelial potential of the retinal pigment epithelium, suggesting the involvement of disrupted tight junctions and impaired active transport of fluid/ions in MEKi-associated retinopathy. The latter may be the major cause of SRDs as we observed that fluid leakage in angiography was absent in the areas of the patients' SRDs.

Successful treatment with daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome: a case report.

BACKGROUND: Transplant-eligible patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome are treated with induction therapy and autologous stem cell transplantation. Conventional induction therapies may exacerbate neuropathy and a high rate of disease progression within 5 years. Furthermore, only 50% of patients are able to walk independently after the therapies. Daratumumab, lenalidomide, and dexamethasone therapy has been reported as a less neurotoxic, highly effective therapy for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome who are ineligible for transplant or whose syndrome is relapsed/refractory, but no reports have provided data from untreated transplant-eligible patients. CASE PRESENTATION: A 34-year-old Japanese woman displayed weakness, pain and edema in the lower limbs, decreased grip strength, amenorrhea, and abdominal distention. She was unable to walk independently. The patient was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and performed four courses of daratumumab, lenalidomide, and dexamethasone therapy, which enabled her to walk independently and did not exacerbate the neuropathy. Hematopoietic stem cells were collected using plerixafor and filgrastim in combination. Autologous stem cell transplantation was performed with high-dose melphalan. At 3-month post-transplantation follow-up, most of her clinical symptoms had disappeared. CONCLUSIONS: Daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation may be more effective than conventional therapy for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome. Although there was concerns that daratumumab, lenalidomide, and dexamethasone therapy might lead to poor mobilization of hematopoietic stem cells, this was overcome with the combination of plerixafor and filgrastim. The benefit of daratumumab, lenalidomide, and dexamethasone as induction therapy prior to autologous stem cell transplantation should be confirmed in future clinical trials.

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.

Morphology and fluorescein leakage in diabetic retinal microaneurysms: a study using multiple en face OCT angiography image averaging.

PURPOSE: To investigate the relevance of microaneurysm morphology in optical coherence tomography angiography (OCTA) image averaging and fluorescein leakage in diabetic retinopathy (DR). METHODS: In 38 consecutive patients with DR, ten consecutive 3- × 3-mm fovea-centered OCTA (HS100, Canon Inc., Tokyo, Japan) and fluorescein angiography (FA) were performed, and averaged OCTA images were created based on the 10 images. After detecting all microaneurysms in FA images, the morphology was classified into four types (focal bulge, saccular/pedunculated, fusiform, and mixed) using averaged OCTA images. The correlation between microaneurysm leakage in FA, retinopathy stage, and microaneurysm morphology was estimated. RESULTS: Thirty-eight eyes (50.0%) of the 33 patients were available for analysis, and 370 (63.5%) of the 583 FA-detected microaneurysms were morphologically classifiable (focal bulge, 46; saccular/pedunculated, 143; fusiform, 29; and mixed, 152) in OCTA. There was a significant correlation between stage and percentage of microaneurysm morphology and between morphology and the presence of leakage (P < 0.0001 and P < 0.01, respectively). The proportion of focal bulges decreased with stage progression, while the other three types increased with stage progression. The percentage of FA leakage for focal bulge, saccular/pedunculated, fusiform, and mixed was 41.3%, 66.4%, 82.8%, and 66.4%, respectively, and the fusiform type showed significant FA leakage. CONCLUSION: Microaneurysm morphology is correlated with the DR stage and FA leakage. Microaneurysm morphology recognition using OCTA image averaging may be useful for the clinical evaluation of DR.

Postoperative follow-up of submacular hemorrhage displacement treated with vitrectomy and subretinal injection of tissue plasminogen activator: ultrawide-field fundus autofluorescence imaging in gas-filled eyes.

PURPOSE: To investigate the utility of Optos ultrawide-field fundus autofluorescence (UWF-FAF) imaging for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal tissue-plasminogen activator (t-PA) injection for subretinal hemorrhage (SRH) displacement. STUDY DESIGN: Retrospective consecutive case series. METHODS: This study included 24 eyes with SRH. Vitrectomy with subretinal t-PA injection was performed, followed by postoperative prone positioning. FAF images acquired using Optos California were examined and the SRH occupancy in the macula was calculated. The main outcome measures were displacement rate and direction of SRH for 3 days postoperatively, and postoperative best-corrected visual acuity (BCVA). RESULTS: The postoperative BCVA ranged from improvement (23 eyes; 95.8%) to no change (one eye; 4.2%). Analysis was done using postoperative Optos FAF images for 20 eyes (83.3%). Postoperative SRH occupancy was significantly reduced, by 27.4%, compared with the preoperative occupancy (P = 0.03). A statistically significant reduction was found between the preoperative and postoperative day (POD)1 (P = 0.04), but not between POD1 and POD2 (P = 0.7), or between POD2 and POD3 (P = 1.0). CONCLUSION: UWF-FAF imaging is useful for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal t-PA injection for SRH displacement.

Serous retinal detachment accompanied by pachychoroid in hypotony maculopathy after trabeculectomy for diabetic neovascular glaucoma.

PURPOSE: Two diabetic case reports of serous retinal detachment (SRD) accompanied by pachychoroid in hypotony maculopathy after trabeculectomy for neovascular glaucoma (NVG). OBSERVATIONS: Case 1: A 66-year-old female with stage 3 NVG and decreased vision acuity in the left eye. After trabeculectomy, postoperative laser suture lysis (LSL) resulted in development of hypotony maculopathy, followed by pachychoroid and SRD. Injection of C3F8 gas in the anterior chamber was unsuccessful and transconjunctival scleral re-suturing was performed. Intraocular pressure (IOP) consequently increased and SRD improved. Case 2: A 60-year-old man with stage 2 NVG and decreased vision acuity in the right eye. Trabeculectomy was uneventful, but postoperative LSL also resulted in development of hypotony maculopathy followed by pachychroid and SRD. Intravitreal bevacizumab injection had no effect and transconjunctival flap re-suturing was performed. IOP consequently increased and SRD improved. CONCLUSIONS: SRD accompanied by pachychoroid was observed in hypotony maculopathy in diabetic cases. VEGF-independent exudative change in hypotony maculopathy may be due to hydrostatic pressure elevation in choroidal blood vessels based on Starling's hypothesis with the consequent breakdown of retinal pigment epithelium barrier in diabetic patients.