FIVE-YEAR VISUAL OUTCOME OF TREATMENT FOR RETINOPATHY OF PREMATURITY IN INFANTS WEIGHING <500 G AT BIRTH: A Multicenter Cohort Study From J-CREST.

PURPOSE: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies. METHODS: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment. RESULTS: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes. CONCLUSION: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.

Comparison of long-term treatment outcomes of laser and anti-VEGF therapy in retinopathy of prematurity: a multicentre study from J-CREST group.

OBJECTIVES: To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP). METHODS: This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses. RESULTS: The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively). CONCLUSIONS: In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment.

Transient Increase of Flicker Electroretinography Amplitudes after Cataract Surgery: Association with Postoperative Inflammation.

Purpose: To determine the characteristics and cause of the increase in the amplitude of flicker electroretinography (ERG) after cataract surgery. Design: Prospective, observational clinical study. Participants: Thirty patients who underwent cataract surgery. Methods: Flicker ERGs were recorded with the RETeval system without mydriasis. The central macular thickness (CMT) was measured by OCT and the aqueous flare value (AFV) by laser flare-cell photometry. These examinations were performed before surgery and 1 day, 1 week, 1 month, 2 months, and 3 months after surgery. Linear regression analysis through the origin was used to compare the correlations between the relative changes in flicker ERG amplitudes and the changes in the CMT and AFV at different times after the surgery. Main Outcome Measures: The amplitude of flicker ERGs, CMT, and AFV. Results: The mean amplitude of flicker ERGs increased significantly by 31% at 1 week after surgery (P < 0.001); a significant increase in the amplitudes was not present at 3 months after the surgery. The mean AFV was significantly increased at 1 day after surgery (P < 0.001), and the CMT was significantly increased at 1 to 3 months after surgery (P < 0.001). The changes in flicker ERG amplitudes at 1 week after surgery were significantly associated with the changes in the CMT at 1 to 3 months after surgery (P < 0.05), and they were weakly associated with the changes in AFV at 1 day after surgery (P = 0.05). Conclusions: These results suggest that the increase in the amplitude of flicker ERGs after cataract surgery is a transient phenomenon that has a peak at 1 week after surgery. The increase of flicker ERG amplitude was associated with measures that are frequently used to evaluate postoperative inflammation. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Response to Initial Anti-Vascular Endothelial Growth Factor for Diabetic Macular Edema Is Significantly Correlated with Response to Third Consecutive Monthly Injection.

Purpose: To determine whether the response to the initial anti-vascular endothelial growth factor (anti-VEGF) injection to treat diabetic macular edema (DME) is significantly correlated with the response to the third consecutive monthly injection of the same anti-VEGF agent. Methods: Seventy eyes with DME that were treated with an anti-VEGF agent (16 eyes with 1.25-mg bevacizumab, 35 eyes with 0.5-mg ranibizumab, and 19 eyes with 2.0-mg aflibercept) were studied. They were treated with three consecutive monthly injections of one of the three anti-VEGF agents. The best-corrected visual acuity (BCVA) in the logarithm of the minimum angle of resolution (logMAR units) and the central macular thickness (CMT) were measured at the baseline, 1 week after the initial injection, and 1 month after the third consecutive monthly injection. The changes of both values from the baseline 1 week after the initial injection (day 7) and 1 month after the third monthly injection were determined. The significance of the correlations between the BCVA and the CMT was determined. Results: The mean BCVA improved significantly for all three agents (0.38 ± 0.22 logMAR units at the baseline to 0.27 ± 0.25 logMAR units) after the three monthly injections (p < 0.05, repeated ANOVA). For all cases, a moderate but significant correlation was found between the BCVA at day 7 and 1 month after the third injection (r = 0.58, p < 0.01; Spearman's rank correlation). No significant correlation was found for bevacizumab (r = 0.09, p = 0.73), moderate correlation was found for ranibizumab (r = 0.42, p < 0.05), and a strong correlation was found for aflibercept (r = 0.83, p < 0.001) between the BCVA at day 7 and at 1 month after the third injection. The mean CMT improved significantly for all three agents (481.9 ± 96.3 µm at the baseline to 364.1 ± 116.0 µm after the three monthly injections, p < 0.05), and a moderate correlation was found for the three agents between CMT at day 7 to that at one month after the third anti-VEGF injection (r = 0.54, p < 0.01). A moderate correlation was found for all three agents between CMT at day 7 to that at one month after the third anti-VEGF injection (r = 0.68 for bevacizumab, r = 0.41 for ranibizumab and r = 0.53 for aflibercept, p < 0.05). Conclusions: The significant correlations between the results on day 7 to that one month after the third anti-VEGF treatment for DME indicates that the long-term effects of anti-VEGF therapy can be predicted by the short-term response. In addition, the results indicate that there may be differences in the effectiveness between the three anti-VEGF agents.

Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema in Eyes with Branch Retinal Vein Occlusion with vs Without Glaucoma - Does Glaucoma Affect Visual Outcome in Eyes with BRVO-ME After antiVEGF Injections?

Purpose: To compare the therapeutic effects of anti-vascular endothelial growth factor (anti-VEGF) agents in eyes with macular edema associated with branch retinal vein occlusion (BRVO-ME) with glaucoma to those without glaucoma. Patients and Methods: This retrospective study was conducted using the medical records of Mie University Hospital from 2013 to 2017. Patients were recruited if they had received anti-VEGF agents for BRVO-ME treatment and included 30 patients (30 eyes) without glaucoma (G[-] group) and 27 patients (27 eyes) with glaucoma (G[+] group). The central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at 3 months after a single injection of anti-VEGF agents were compared between the two groups. Results: Before treatment, the mean±standard deviation of the CRT was 514.2±117.3 µm for the G[-] group, which was not significantly different from that for the G[+] group (533.4±171.4 µm). The CRT in the G[-] and G[+] groups significantly reduced to 321.1±114.6 µm and 347.8±134.7 µm, respectively, at 1 month after the injection and to 360.4±159.5 µm and 352.4±151.9 µm, respectively, at 3 months after the injection (P<0.01 for each group). The difference in the degree of CRT reduction between the two groups was not significant. Before treatment, the BCVA was 0.42±0.32 logMAR units in the G[-] group and 0.57±0.33 logMAR units in the G[+] group, showing no significant difference. The BCVA in the G[-] and G[+] groups improved significantly to 0.27±0.26 logMAR units and 0.34±0.42 logMAR units, respectively, at 1 month, and to 0.18±0.20 logMAR units and 0.39±0.34 logMAR units, respectively, at 3 months (P<0.01). The BCVA in the G[-] group was significantly better than that in the G[+] group at 3 months (P=0.02). Conclusion: The therapeutic response of anti-VEGF agents for BRVO-ME is affected by the presence of glaucoma.

Correction: Sugimoto et al. Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan. J. Clin. Med. 2022, 11, 165.

In the original publication [...].

Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan.

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.

Clinical preferences and trends of anti-vascular endothelial growth factor treatments for diabetic macular edema in Japan.

AIMS/INTRODUCTION: To determine the current clinical preferences of anti-vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan. MATERIALS AND METHODS: This was a descriptive cross-sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists. RESULTS: The results showed that 81.2% preferred intravitreal injections of anti-VEGF antibodies as the first-line therapy. The most important indicators for beginning anti-VEGF therapy were: the best-corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti-VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub-Tenon steroid injection were preferred. The contraindications for anti-VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti-VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately. CONCLUSIONS: Our results present the current clinical preferences of anti-VEGF treatment for DME in Japan. The best-corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti-VEGF treatment as first-line therapy and prefer the 1 + pro re nata regimen.

Annual incidences of visual impairment during 10-year period in Mie prefecture, Japan.

PURPOSE: To determine the annual incidence of visual impairment in a Japanese population during a 10-year period. METHODS: We examined the physical disability certificates issued yearly between 2004 and 2013 in Mie prefecture, Japan. During this period 2468 visually impaired people were registered under the newly defined Act on Welfare of the Physically Disabled Persons' criteria. The age, sex distribution, and causes of visual impairment were determined from the certificates. RESULTS: The major causes of visual impairment during the ten-year period were glaucoma (23.3%), diabetic retinopathy (17.3%), retinitis pigmentosa (12.2%), macular degeneration (9.0%), chorioretinal degeneration or high myopia (7.4%), optic atrophy (5.8%), stroke or brain tumor (5.4%) and cataracts (3.7%). The incidence of glaucoma was significantly higher throughout the period (2004-2013), and that of diabetic retinopathy was lower between 2007 and 2013. The incidence of retinitis pigmentosa did not change significantly during the 10-year period. The incidence of macular degeneration tended to increase between 2004 and 2007, but it decreased significantly between 2007 and 2013. CONCLUSIONS: The results indicate that in Japan, the rates of the major causes of visual impairment altered in the most recent 10-year period reflecting the recent changes in the social background and advances in ocular and systemic treatment.

A Case of Sustained Intraocular Pressure Elevation after Multiple Intravitreal Injection of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.

RPE65 Mutations in Two Japanese Families with Leber Congenital Amaurosis.

PURPOSE: To investigate genetic and clinical features of patients with Leber congenital amaurosis (LCA) caused by RPE65 mutations. METHODS: Five Japanese families with LCA were recruited. We performed complete ophthalmic examinations, with optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Genetic analysis was performed with whole-exome sequencing analysis and Sanger sequencing. RESULTS: We identified RPE65 mutations in two unrelated LCA patients from two families. Case 1: A 5-month-old girl was diagnosed with LCA because of nystagmus, loss of vision and non-recordable ERG. She was the only one affected in her non-consanguineous family, and exhibited novel compound heterozygous RPE65 mutations (c.177C>G, p.H59Q and c.183_184insT, p.D62X). Case 2: A 30-year-old woman, who had night blindness and poor ocular pursuit during the first year of life, exhibited severe retinal degeneration and non-recordable ERG. She was the only affected in her non-consanguineous family, and showed a homozygous RPE65 mutation (c.1543C>T, p.R515W). CONCLUSIONS: By using whole-exome sequencing analysis, three RPE65 mutations were identified in two Japanese patients with LCA. This approach would be useful for identification of disease-causing mutations of LCA.

Changes in angle of optic nerve and angle of ocular orbit with increasing age in Japanese children.

PURPOSE: To study changes in the opening angle of the optic nerve and the angle of the ocular orbit with increasing age in normal Japanese children. METHODS: We studied 147 normal children (aged 6 months to 18 years) who had undergone CT as a diagnostic procedure. Measurements were performed on axial CT images that included the entire optic nerve of both eyes. The opening angle of the optic nerve was defined as the angle formed by the intersection of a line running through the left optic nerve and a vertical line passing through the centre of the nose. The opening angle of the orbit was defined as the angle formed by the intersection of a line running tangentially along the deep lateral wall of the left orbit and a vertical line passing through the centre of the nose. The relationship between age and these opening angles was analysed by regression analysis. RESULTS: The correlation between age and opening angle of the optic nerve was not significant. In contrast, the opening angle of the orbit decreased relatively rapidly until about 2-3 years of age, and then it stabilised. The decrease in the opening angle of the orbit with increasing age was significant (p<0.001). The relationship between these two parameters was best fitted by a logarithmic regression curve. CONCLUSIONS: Because the opening angle of the orbit decreased significantly with increasing age, this factor must be considered when diagnosing and treating strabismus in children.

Bilateral retinal detachment in Werner syndrome.

PURPOSE: To report the development of bilateral retinal detachment in a patient with Werner syndrome. METHODS: Retrospective chart review. A 44-year-old woman diagnosed with Werner syndrome developed bilateral retinal detachment. The fundus in both eyes showed patchy chorioretinal atrophy similar to that seen in high myopia, with the retinal detachment limited to the posterior pole. Two weeks after performing vitrectomy in the right eye, vitrectomy was performed in the left eye. RESULTS: After the surgeries, both retinas were reattached. During the surgeries, we observed an excessively liquefied vitreous and a posterior hyaloid membrane that was tightly attached to the retina. The retinal break was located along the superotemporal arcade and over an area of the patchy chorioretinal atrophy in both eyes. The chorioretinal atrophy and vitreous liquefaction appeared to be excessive for the patient's age and axial lengths (right: 26.66 mm, left: 27.04 mm). CONCLUSION: Vitreoretinal changes found in this case might have been partially because of the premature aging associated with Werner syndrome.

Peripheral capillary nonperfusion and full-field electroretinographic changes in eyes with frosted branch-like appearance retinal vasculitis.

We report a patient with frosted branch-like appearance retinal vasculitis associated with peripheral capillary nonperfusion and full-field electroretinographic changes. A 62-year-old man presented with sudden bilateral decreased vision accompanied by headaches. His best-corrected visual acuity was 0.01 in both eyes. Fundus examination and fluorescein angiography showed bilateral frosted branch-like appearance retinal vasculitis, and spectral-domain optical coherence tomography showed severe macular edema in both eyes. The cerebrospinal fluid analyses showed an increased lymphocyte count and protein levels. He was treated with systemic corticosteroid therapy, and his best-corrected visual acuity improved to 0.8 OD and 1.0 OS at 6 months after onset. However, fluorescein angiography showed a lack of capillary perfusion in the periphery, and the oscillatory potentials on full-field electroretinography were severely reduced in both eyes. These findings indicated extensive retinal ischemia and inner retinal dysfunction, and that fluorescein angiography and full-field electroretinograms can be useful during follow-up of eyes with frosted branch-like appearance retinal vasculitis.

[Causes of visual impairment in Mie Prefecture during a 5-year period].

PURPOSE: The purpose of this study was to determine the causes of visual impairment in Mie prefecture during a five-year period. SUBJECTS AND METHODS: The study was conducted between April 2004 and March 2009 in Mie Prefecture. 1,322 visually impaired people as defined by the Act on Welfare of Physically Disabled Persons were enrolled. We reviewed age, sex, causes of visual impairment, degree of disability and medical conditions according to their physical disability certificate. RESULTS: The four major causes of visual impairment were glaucoma (20.3%), diabetic retinopathy (18.9%), retinitis pigmentosa (12.2%), and macular degeneration (9.1%), followed by chorioretinal degeneration, stroke or brain tumor, optic atrophy, and cataract. The average ages of the four major causes were glaucoma (77.1 years), diabetic retinopathy (65.1 years), retinitis pigmentosa (62.5 years) and macular degeneration (77.7 years). CONCLUSIONS: The most common cause of visual impairment in Mie prefecture was glaucoma. The four major causes in Mie prefecture were the same as the results of the nation-wide investigation reported in 2006.