INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

Alteration of treatment choices and the visual prognosis for diabetic macular edema in the era of anti-VEGF drugs: Analysis of the STREAT-DME 2 study.

PURPOSE: To assess the real-world outcome of best-corrected visual acuity (BCVA) following 2-year intervention for treatment-naïve diabetic macular edema (DME) since the approval of anti-vascular endothelial growth factor (VEGF) therapy. METHODS: A total of 1,780 treatment-naïve eyes with DME for which intervention was initiated between 2015 and 2019, and which were followed for 2 years, were extracted from the longitudinal medical records of 37 retinal disease institutions in Japan. Interventions included anti-VEGF therapy, topical corticosteroid therapy, macular photocoagulation, and vitrectomy. The baseline and final BCVA, and the number and timing of interventions were recorded. Eyes were classified according to the year in which intervention was initiated. RESULTS: Over a 2-year period, BCVA improved annually, finally reaching 7 letters. The proportion of eyes in which good vision was maintained (BCVA >20/40) increased to 73.3% in the latest period. The administration of anti-VEGF therapy remained stable, accounting for approximately 90% of eyes. Notably, the proportion of eyes receiving anti-VEGF drugs as first-line treatment increased dramatically to approximately 80%. CONCLUSION: Anti-VEGF therapy has become the first-line treatment since the approval of anti-VEGF drugs for DME. These findings reflect the evolution of DME treatment and highlight the superiority of anti-VEGF therapy and its increased uptake over time.

Switching to brolucizumab from aflibercept in age-related macular degeneration with type 1 macular neovascularization and polypoidal choroidal vasculopathy: an 18-month follow-up study.

PURPOSE: To assess the effect of switching to brolucizumab from aflibercept on eyes with type 1 macular neovascularization (MNV) and polypoidal choroidal vasculopathy (PCV) at 18 months. METHODS: This study was a retrospective, observational case series that included 19 eyes of 19 patients with type 1MNV and 23 eyes of 22 patients with PCV. We compared the injection intervals, visual acuity, total lesion size, and the number of polypoidal lesions between baseline and 18 months. The correlations between the data including treatment interval, total lesion size, and the number of polyps were also assessed. RESULTS: Treatment intervals were significantly extended; from 7.4 ± 1.4 weeks to 11.6 ± 2.6 weeks for type 1 MNV, p < 0.001; from 6.9 ± 1.3 to 11.7 ± 3.1 weeks for PCV, p < 0.001. In type 1 MNV eyes, strong correlation was found between total lesion size and brolucizumab injection intervals (r = - 0.81; p = 0.0002) and moderate correlation was found between treatment frequency with aflibercept and that with brolucizumab (r = 0.76; p = 0.040). In PCV eyes, we found strong correlation between the number of polyps and brolucizumab treatment frequency (r = - 0.81; p = 0.0016) and moderate correlation between total lesion size and brolucizumab treatment interval (r = - 0.48; p = 0.034). Intraocular inflammation occurred in 2 of 19 eyes (10.3%) with type 1 MNV and 5 of 23 eyes (21.7%) with PCV. CONCLUSION: The properties to extend brolucizumab injection intervals might be the smaller lesion size and lower aflibercept frequency for type 1 MNV and the smaller number of polyps and the smaller size of lesion for PCV.

Using optical coherence tomography angiography to guide myopic choroidal neovascularization treatment: a 3-year follow-up study.

PURPOSE: To report the long-term changes of the size of myopic choroidal neovascularization (mCNV) using optical coherence tomography angiography (OCTA). METHODS: This was a retrospective, observational case study of eleven eyes in eleven patients with mCNV followed with OCTA for a minimum of 3 years. The flow area of mCNV on OCTA, the size of chorioretinal atrophy (CRA) and central choroidal thickness were analyzed. The relationship between the changes of mCNV size and recurrences treated with anti-vascular endothelial growth factor (VEGF) agents was also assessed. RESULTS: Three eyes out of eleven eyes showed enlargement of the mCNV over 3 years. In two of the three eyes, the mCNV recurrences had not been treated immediately (the examination intervals were 4 months and 5 months, respectively), and we found obvious enlargement of the mCNV. In three eyes, the mCNV size decreased in 1 year and was stable thereafter without recurrences. In five eyes, mCNV size did not show remarkable changes for 3 years. In three of the five eyes, no recurrences were detected and two of the five eyes underwent prompt treatments against recurrences. CONCLUSION: Regular examination and prompt treatments against recurrences are critical to prevent enlargement of mCNV.

The association between cone density and visual function in the macula of patients with retinitis pigmentosa.

PURPOSE: We observed cone photoreceptors by using adaptive optics (AO) fundus camera and optical coherence tomography (OCT) in patients with retinitis pigmentosa (RP) and examined the correlations between cone photoreceptors and visual function over 2 years. METHODS: Six patients with RP were studied. All patients underwent measurement using best-corrected decimal visual acuity, OCT, a Humphrey Field Analyzer with the 10-2 test grid pattern, and AO. AO images of the foveal center were obtained using an rtx1™ AO fundus camera, and cone counting was performed at 0.5 mm from the foveal center. RESULTS: AO detected a decrease of cone density over 2 years in RP patients. However, visual acuity, foveal sensitivity, and photoreceptor thickness were not changed over the 2 years. CONCLUSIONS: AO images showed a decrease in the number of foveal cone densities over 2 years in patients with RP. AO may shorten the period required to predict the RP progression rate.

Baerveldt® glaucoma implant surgery with the double scleral flap technique to prevent Hoffman elbow exposure.

OBJECTIVE: To compare the efficacy and safety of the Baerveldt® glaucoma implant (BGI) between a preserved donor scleral patch alone and double scleral flaps, comprising a preserved donor scleral patch and an autologous scleral pedicle flap. METHODS: This was an open-label retrospective study. We analyzed the cases of 52 consecutive patients (56 eyes) who underwent BGI surgery with the Hoffman elbow (#BG 102-350, Abbott) and were followed up for >1 year. Twenty-one eyes underwent BGI surgery with a preserved donor scleral patch alone (donor-patch group), and the other 35 eyes underwent BGI surgery with a preserved donor scleral patch and an autologous scleral pedicle flap (double-flap group). The main outcome was the incidence of Hoffman elbow exposure associated with each surgical approach. RESULTS: Three patients in the donor-patch group (14.3%) developed Hoffman elbow exposure, whereas in the double-flap group, no cases had Hoffman elbow exposure (p = 0.048). CONCLUSIONS: The use of the double scleral flaps technique was more efficient in preventing Hoffman elbow exposure.

Correlation between outer retinal layer thickness and cone density in patients with resolved central serous chorioretinopathy.

PURPOSE: We aimed to observe photoreceptors and outer retinal layer thickness by using an adaptive optics (AO) fundus camera and spectral domain optical coherence tomography (SD-OCT) in patients with central serous chorioretinopathy (CSC). METHODS: Twelve eyes of 12 patients with resolved CSC were studied. After subretinal fluid (SRF) had resolved, AO images of the macula were obtained by using the rtx1TM AO fundus camera (Imagine Eyes, France). Cones in the nasal and temporal areas of the macula, 0.5 mm from the foveal center, were counted. Outer retinal layer thickness was measured as the distance between the outer border of external limiting membrane (ELM) and the inner border of retinal pigment epithelium (RPE) at 0.5 mm from the foveal center. The first measurement was performed after resolution of the subretinal fluid and was defined as the baseline. Then, the second measurement was performed in the same location after 12 months. RESULTS: In the eyes with resolved CSC, the mean logMAR values of visual acuity at baseline and 12 months were 0.16 and 0.01, respectively (p = 0.0023). The mean cone densities at baseline and 12 months were 12,213 and 17,146 cones/mm2, respectively. The mean cone densities at 12 months were significantly increased compared to baseline (p = 0.0014). The mean outer retinal layer thickness at baseline (53.5 µm) was significantly thinner than that at 12 months (60.7 µm) (p = 0.0013). The mean cone densities were significantly correlated with outer retinal layer thickness and logMAR visual acuity. CONCLUSIONS: Adaptive optics imaging revealed a gradual increase in the number of macular cone densities during 12 months in patients with resolved CSC, which was correlated with outer retinal layer thickness and visual acuity in a short term.

Compared to Trabeculectomy, Ex-Press® Surgery Significantly Decreased the Loss of Corneal Endothelial Cell Density in Low-Intraocular-Pressure Glaucoma: 3-Year Follow-Up.

Purpose: We compared the corneal endothelial cell loss between trabeculectomy (Trab) and Ex-Press® surgery (EXP) for low-intraocular pressure (IOP) glaucoma patients. Patients and Methods: This was a single-facility retrospective study. We analyzed the cases of patients with primary open-angle glaucoma (POAG) and pre-operative IOP ≤ 21 mmHg who had undergone Trab or EXP surgery and were followed for >3 years. Noncontact specular microscopy was used to determine the corneal endothelial cell density (CED) before and after Trab or EXP surgery. We measured the CED at 12, 24, and 36 months post-surgery. We compared the CED values and CED survival ratio after both surgeries using paired t-tests. Results: We included 39 eyes that underwent Trab and 36 eyes that underwent EXP surgery. In the Trab group, the mean CED value had decreased from 2333 ± 399 at baseline to 2066 ± 587 cells/mm2 after 3 years. In the EXP group, the mean CED value had decreased from 2320 ± 393 at baseline to 2229 ± 460 cells/mm2 after 3 years. The survival ratio of CED at >3 years was 89.3 ± 14.2% (Trab group) and 95.6 ± 11.1% (EXP group); compared to the Trab surgery, the EXP surgery thus significantly decreased the CED loss (p = 0.037). No case resulted in bullous keratopathy. Conclusion: Compared to trabeculectomy, Ex-Press® surgery appears to be a safer surgical method with regard to the endothelial cell loss risk.

Bilateral Serous Retinal Detachment Associated with a Mitogen-activated Protein KinaseKinase Inhibitor in a Patient with BRAF-mutant Colorectal Cancer.

We herein report a 73-year-old woman with BRAF V600E-mutated colon cancer treated with encorafenib plus cetuximab with binimetinib as standard salvage therapy for patients with advanced colorectal cancer. She developed bilateral serous retinal detachment the next day, and the regimen was discontinued, resulting in complete resolution by the third day. Doublet therapy without binimetinib was initiated along with a weekly ophthalmologic examination for 10 weeks without recurrence of retinal detachment. Thus, binimetinib was presumed to have been the cause of the retinal detachment. This clinical course suggests the need for close monitoring of patients for vision impairment and close collaboration with ophthalmologists.

Hydroxychloroquine's Early Impact on Cone Density.

PURPOSE: To evaluate early effects of hydroxychloroquine (HCQ) on the retina using adaptive optics (AO). METHODS: This was a prospective observational single-center study of 29 eyes of 29 patients who had been treated with HCQ for the first time and followed with AO for a minimum of two years. Cone counting was performed in 4 quadrants, nasal, temporal, superior, and inferior, at 0.75 mm from the foveal center. The changes of cone density on AO, visual acuity, and foveal thickness within two years of use were analyzed. The changes of mean cone density of patients whose cumulative dose was over 200 g in 2 years were also assessed. We evaluated the correlation between cone density and cumulative dose of HCQ. RESULTS: There was no significant decrease in cone density in the first 2 years of HCQ use. VA and foveal thickness did not show obvious change, either. Among 9 patients whose cumulative dose was over 200 g in 2 years, the mean cone density showed no significant change at 6, 12, 18, and 24 months compared with baseline (P=0.381, P=0.380, P=0.281, and P=0.534, respectively). There was no correlation between cone density and cumulative dose of HCQ at two years (Spearman's correlation coefficient, r = -0.0553, P=0.780; n = 29). CONCLUSION: AO showed no change in cone density in the first two years of HCQ use.

The relationship between vascular endothelial dysfunction and treatment frequency in neovascular age-related macular degeneration.

PURPOSE: To assess the correlation between endothelial dysfunction and frequency of antivascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD). METHODS: We examined 64 consecutive patients with nAMD who were evaluated for endothelial function by use of peripheral arterial tonometry (EndoPAT 2000; Itamar Medical, Caesarea, Israel) at Toyama University Hospital from January 2015. We tallied the number of anti-VEGF treatments between January 2014 and December 2015 and determined the correlation between the number of anti-VEGF injections and endothelial function expressed as the reactive hyperemia index (RHI). Multiple regression analysis was also performed to identify the independent predictors of a larger number of injections. RESULTS: The mean number of anti-VEGF injections was 8.2 ± 3.3. The mean lnRHI was 0.47 ± 0.17. The lnRHI correlated with the number of anti-VEGF injections (r = -0.56; P = 0.030). The multiple regression analysis revealed that endothelial function, neovascular subtypes, and treatment regimens were associated with the number of injections. CONCLUSIONS: Endothelial dysfunction may affect the efficacy of anti-VEGF therapy. Neovascular subtypes may also predict a larger number of injections.

Analysis of retinal vessels in eyes with retinitis pigmentosa by retinal oximeter.

PURPOSE: To study changes in the oxygen saturation and calibre of retinal vessels in the eyes of patients with retinitis pigmentosa (RP). METHOD: In this cross-sectional study, 63 eyes of 63 patients with RP and 14 eyes of 14 healthy subjects were enrolled and examined at Toyama University Hospital. Retinal oximetry measurements were performed using a spectrophotometric oximetry unit (Oxymap T1, Reykjavik, Iceland), which is coupled to a fundus camera base (TRC-50DX; Topcon Corporation, Tokyo, Japan). Retinal arterioles of 28 eyes and retinal venules of 35 eyes with adequate image quality were selected for analyses. We calculated the residual areas of visual field (I-4e and V-4e isopters) in each eye and determined the correlations between the data of retinal vessels and the areas of visual field in the RP eyes. RESULTS: The mean oxygen saturation of the venules in the RP eyes (60.2 ± 6.5%) was significantly higher than that in healthy eyes (54.6 ± 6.3%, p = 0.0089). The oxygen saturation of the venules in the RP eyes correlated significantly with the residual areas of the visual field of V-4e (r = -0.50; p = 0.0030). The mean calibres of the retinal arterioles (91.1 ± 9.1 µm) and retinal venules (116 ± 13 µm) of the RP eyes were significantly narrower than those of the healthy eyes (115 ± 11 µm and 152 ± 15 µm, respectively, p < 0.01). The retinal arteriolar and venular calibres in the RP eyes correlated with the residual areas of the visual field of V-4e (r = 0.43; p = 0.033 and r = 0.45; p = 0.011, respectively). CONCLUSIONS: The severity of RP was correlated with increased oxygen saturations in the retinal venules and decreased retinal vessel calibres.

Microperimetric Biofeedback Training Improved Visual Acuity after Successful Macular Hole Surgery.

Purpose. To evaluate the efficacy of setting a preferred retinal locus relocation target (PRT) and performing Macular Integrity Assessment (MAIA) biofeedback training in patients showing insufficient recovery of best corrected visual acuity (BCVA) despite successful closure of an idiopathic macular hole (MH). Methods. Retrospective interventional case series. Nine eyes of 9 consecutive patients with the decimal BCVA of less than 0.6 at more than 3 months after successful MH surgery were included. A PRT was chosen based on MAIA microperimetry and the patients underwent MAIA biofeedback training. BCVA, reading speed, fixation stability, and 63% bivariate contour ellipse area (BCEA) were evaluated before and after the training. Statistical analysis was carried out using paired Student's t-test. Results. PRT was chosen on the nasal side of the closed MH fovea in 8 patients. After the MAIA training, BCVA improved in all patients. The mean logMAR value of BCVA significantly improved from 0.33 to 0.12 (p = 0.007). Reading speed improved in all patients (p = 0.29), fixation stability improved in 5 patients (p = 0.70), and 63% BCEA improved in 7 patients (p = 0.21), although these improvements were not statistically significant. Conclusion. MAIA biofeedback training improved visual acuity in patients with insufficient recovery of BCVA after successful MH surgery.

Near-infrared fundus autofluorescence-visualized melanin in the choroidal abnormalities of neurofibromatosis type 1.

PURPOSE: To report a series of three cases of neurofibromatosis type 1 examined by near-infrared fundus autofluorescence (NIR-AF) with a scanning laser ophthalmoscope and spectral-domain optical coherence tomography (OCT) to show the characteristics of choroidal abnormalities. METHODS: Retrospective case series. Six eyes of three patients were examined by conventional fundus examinations, near-infrared monochromatic light reflectance (NIR-R) and NIR-AF, OCT, fluorescein angiography, and indocyanine green angiography. RESULTS: All eyes showed multiple bright patchy regions in the choroid of the posterior pole with NIR-R. NIR-AF revealed high fluorescent regions of similar sizes at fundus locations identical to those shown by NIR-R. In one case, hypofluorescent regions were shown by indocyanine green angiography in the bright fluorescent region shown by NIR-AF. The other two cases showed no abnormality under conventional fundus examination or fluorescein angiography. OCT images crossing the bright patchy region showed irregular hyper-reflectivity in the choroid in two cases and hyporeflectivity in one case. CONCLUSIONS: NIR-AF demonstrated that dense melanin was included in the choroidal nodules of neurofibromatosis type 1. The choroidal nodules showed hyper- or hyporeflectivity in the choroid on OCT, which did not affect the retinal structure.