Japanese Journal of Ophthalmology最新文献

Purpose: The aim of this study was to investigate the vascular characteristics of pediatric patients with familial Mediterranean fever (FMF) with homozygous c.~(p.M694V) mutations in the MEFV gene by comparing their retinal vascular densities with those of healthy controls by use of optical coherence tomography angiography (OCTA).

Study design: Prospective observational study.

Methods: A total of 80 participants, 35 FMF pediatric patients and 45 healthy controls, were included in the study. The baseline demographic and clinical characteristics were examined, and OCTA was used to assess vascular densities in various regions of the superficial and deep capillary plexus (DCP) and optic disc. Statistical analyses were performed to identify significant differences between the groups.

Results: The study demonstrated that patients with FMF exhibited a significant reduction in vascular density within the parafoveal deep capillary plexus (DCP) (P = 0.047). Additionally, vascular density in the inferior and temporal subregions of the perifoveal DCP was significantly lower in the FMF group than in the controls (P = 0.038 and P = 0.027, respectively), with a similar trend observed for the overall perifoveal DCP vascular density (P = 0.025). In addition, optic disc vascular density was significantly lower in the FMF patients than in the healthy controls (P = 0.026). Approximately 60% of the FMF patients had severe disease symptoms, whilst 40% of them had mild symptons.

Conclusions: The findings suggest significant reductions in deep capillary plexus and optic disc vascular density in children with FMF, further suggesting an underlying vascular pathology related to this autoinflammatory disease. Regular ophthalmic evaluations are necessary to monitor potential effects on retinal health in pediatric FMF patients, even when anterior segment examination findings are normal.

Purpose: Juvenile onset open-angle glaucoma (JOAG) typically affects individuals under 40 years of age, causing a rise in intraocular pressure that results in considerable damage to the optic nerve. To expand the spectrum of mutations linked to JOAG and explore their structural consequences, we examined the genetic alterations within the SIX6 gene.

Study design: We focused on assessing the whole coding region of the SIX6 gene and the clinical significance of the common SIX6 gene single nucleotide polymorphisms (SNP) rs10483727 and rs33912345, specifically analyzing its association with key clinical factors, including intraocular pressure (IOP), visual acuity, and the vertical cup-to-disc ratio (VCDR).

Method: The study included 111 unrelated patients with confirmed JOAG and 100 healthy adult controls without any ocular or systemic conditions. The patients initially underwent genetic screening for pathogenic variants in the CYP1B1, MYOC, and OPTN genes. Individuals who tested negative for pathogenic variants in these three genes (n=81) were subsequently screened for variants in the SIX6 gene while all 111 patients and 100 control samples were screened for SNPs to strengthen the statistical correlation. Identified sequence variations were searched in the ClinVar databases, HGMD, and dbSNP. Six different online available algorithms including REVEL, SIFT, CADD, Mutation Taster, IMutant2.0, and MetaLR were used for the pathogenicity prediction of missense variations. The Structural consequences of detected possible pathogenic variations were predicted by using PyMol, Chimera and molecular dynamics (MD) simulation of these changes. Statistical analyses assessed the association of rs33912345 with disease phenotypes.

Results: Sanger sequencing identified seven nucleotide variants in the SIX6 gene, including five missense and two synonymous variants. Two missense variants, p.(A99G) and p.(S156R), were predicted to be pathogenic. The novel variant p.(A99G) was absent in controls and demonstrated significant structural disruption, with altered intramolecular interactions and steric clashes. Homology analysis revealed high evolutionary conservation at the mutated positions, highlighting their functional significance. MD simulations confirmed altered stability in the mutant proteins. Logistic regression linked rs33912345 to JOAG, with significant associations observed for IOP (p = 0.01538), and VCDR (p = 0.019).

Conclusion: This study identified novel and known pathogenic variants in the SIX6 gene that may contribute to JOAG pathogenesis. Structural and functional analyses suggest that these mutations disrupt protein function. The findings enhance our understanding of JOAG genetics and may aid in early diagnosis and therapeutic targeting.

Purpose: To evaluate long-term outcomes for polypoidal choroidal vasculopathy (PCV) in Japanese patients in the EVEREST II study.

Study design: A multicenter, cross-sectional study of the long-term outcomes of a cohort of patients originally treated with ranibizumab alone (monotherapy group) or in combination with photodynamic therapy PDT (combination group) in the EVEREST II study (ClinicalTrials.gov identifier, NCT01846273).

Methods: Ninety participants from the six-year EVEREST II follow-up: 20 Japanese and 70 non-Japanese were included. Long-term changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were reported in the Japanese compared to non-Japanese participants. Number of injections, types of anti-vascular endothelial growth factor (VEGF) agents used, and cases with equal visits and injections, indicating fixed dosing or treat-and-extend (TAE) administration were investigated. Outcomes were also compared between those who had verteporfin PDT during the six-year period (n=14) and those who did not (n=6).

Results: The Japanese and non-Japanese participants had similar baseline characteristics. The mean age for Japanese participants was 76±4.47 years, with 25% being women. BCVA improved from baseline to year 2 in both groups (P < 0.05). At six years, BCVA was maintained in the Japanese (67.2 ETDRS letters) but decreased in the non-Japanese participants (from 68.8 to 53.5 letters). The Japanese participants received more injections than the non-Japanese (12.5 vs. 7.57, P=0.017). Aflibercept was the most frequently used anti-VEGF agent, and the number of fixed dosing or TAE administration was higher in the Japanese participants. No significant differences were found in functional and anatomical outcomes between those who received PDT and those who did not (all P > 0.05). However, non-PDT participants had numerically worse BCVA at the final visit.

Conclusions: This study highlights positive long-term outcomes for Japanese PCV patients and underscores the need for further research to validate these findings in broader patient populations.

Purpose: To report the midterm outcomes of Ahmed glaucoma valve (AGV) implantation and trabeculectomy (Trab) in exfoliative glaucoma (XFG).

Study design: We performed a retrospective comparison analysis of 95 eyes of 81 patients with AGV implantation versus 88 eyes of 82 patients with Trab for XFG up to 3 years.

Method: The intraocular pressure, number of medications, corneal endothelial cell numbers, and surgical complications were analyzed. The cumulative probability of success was analyzed by 5 ≦IOP ≦18 mm Hg and reduction of IOP ≧20% from the preoperative IOP. Kaplan-Meier survival analysis was used to analyze the probability of success and for the comparison between the Trab group and the AGV group.

Results: The cumulative probability of the qualified surgical success rate was higher, but the complete success rate was lower in the AGV group than in the Trab group. AGV insertion for the eyes with a history of Trab failure and for the eyes without a history of previous glaucoma operations showed no significant difference in postoperative IOP. The occurrence of layered hyphema was higher in the AGV group, but the overall occurrence rates of other complications were similar in the 2 groups.

Conclusion: AGV implantation is a reasonable surgical method for XFG, especially for patients with a history of previously failed Trab.

Purpose: Pachychoroid spectrum diseases reportedly progress from central serous chorioretinopathy (CSC) to pachychoroid neovasculopathy (PNV) and polypoidal choroidal vasculopathy (PCV). We investigated and compared choroidal thicknesses in the macular and peripheral areas among eyes with CSC, PNV, and PCV, as well as in normal control eyes.

Study design: Retrospective case-control study.

Methods: We studied 117 consecutive eyes with treatment-naïve pachychoroid spectrum diseases, comprising 52 eyes with CSC, 27 with PNV, and 38 with PCV, along with 106 age-, gender-, and axial length-matched normal control eyes. Widefield choroidal thickness maps generated by widefield optical coherence tomography were quantitatively analyzed. Mean choroidal thickness values in the macular, superotemporal, inferotemporal, superonasal, and inferonasal areas were determined, and then compared among the three pachychoroid spectrum diseases, and also assessed in normal controls.

Results: The mean choroidal thickness reduction with aging was greater in eyes with pachychoroid spectrum diseases than in normal controls across all measured areas. Patient age increased in the order of CSC, PNV, and PCV, whereas there was no significant difference between PNV and PCV (P<0.01, CSC vs. PNV, CSC vs. PCV). Mean choroidal thickness exhibited a progressive decrease from CSC to PNV and PCV across all areas, although there were no significant differences between PNV and PCV (P<0.01, CSC vs. PCV, CSC vs. PNV).

Conclusions: Overall choroidal thickness appears to decrease during the progression of pachychoroid spectrum diseases. This decline might be attributable to reduced choroidal blood flow due to the choriocapillaris attenuation associated with aging and pachychoroid pathophysiology.

Purpose: To investigate factors affecting timing of the first recurrence after three loading aflibercept injections in patients with newly diagnosed neovascular age-related macular degeneration (NAMD).

Study design: Retrospective chart review.

Methods: A retrospective study was conducted on 193 eyes from 193 patients newly diagnosed with NAMD who received monthly three loading aflibercept injections and a fourth injection by pro-re-nata therapy regimen for recurrence between January 2016 and May 2023. Recurrence was defined as reaccumulation of subretinal or intraretinal fluid or new or increased retinal or subretinal hemorrhage. Patients were divided into two groups. One group received a fourth injection within 12 weeks after the third dose of aflibercept (Group A) and the other group received a fourth injection after 12 weeks (Group B).

Results: In group A (65 eyes) compared to group B (128 eyes), the frequency of polypoidal choroidal vasculopathy (PCV) was higher (60.0%: 36.7%), the frequency of retinal angiomatous proliferation was lower (6.2%: 18.0%), and the optical coherence tomography (OCT) findings showed that pigment epithelial detachment (PED) of hollow type was more likely to be observed compared to solid type (OR=3.14, p=0.013) or mixed type (OR=3.67, p=0.003) of PED; sharply peaked PED was more common (OR=2.05, p=0.045) and less likely to be seen in females (OR=0.46, p=0.034).

Conclusion: In patients with newly diagnosed NAMD who received three injection loading doses of aflibercept, earlier recurrence was predicted when PCV was present, when a hollow type of PED was observed on OCT, and when the patient was a man.

Purpose: To investigate the effects of vitamin D replacement therapy on dry eye disease (DED) test parameters in pediatric patients with vitamin D deficiency (VDD).

Study design: Prospective clinical study METHODS: This prospective study included 46 pediatric patients diagnosed with VDD and 39 sex- and age-matched healthy subjects. DED test parameters, including Schirmer test, tear break-up time (TBUT), upper and lower lid meiboscore and meibomian gland loss (MGL), tear meniscus height (TMH), tear meniscus area (TMA), Ocular Surface Disease Index (OSDI), and corneal fluorescein staining score (CFSS) were assessed. The measurements in the VDD group were performed twice, the first time before the treatment and the second time three months after the vitamin D replacement therapy. Only one assessment was made in the control subjects.

Results: Significant improvements were observed in the Schirmer test (p=0.007), TBUT (p=0.03), TMH (p<0.001), TMA (p<0.001), CFSS (p<0.001), and OSDI scores (p=0.016) after vitamin D replacement therapy in children with VDD. Lower eyelid meiboscore and MGL improved significantly after treatment (p=0.022 and p<0.001, respectively), but no significant difference was observed in upper meiboscore and MGL after vitamin D replacement therapy (p=0.986 and p=0.758, respectively). There was no significant difference between the treated VDD group and the healthy controls in Schirmer test, TBUT, TMH, TMA, OSDI scores and lower eyelid meiboscore and MGL (p>0.005 for all).

Conclusion: Vitamin D replacement therapy significantly improves DED test parameters in pediatric patients with VDD.

Purpose: We investigated changes in corneal higher-order aberrations (HOAs) after iStent inject® W implantation combined with cataract surgery.

Study design: Retrospective observational study.

Methods: A total of 41 eyes that underwent this procedure between August 2022 and July 2024 were included. Intraocular pressure (IOP), corneal HOAs, coma-like aberrations, and spherical-like aberrations were measured before and at 1, 2, and 3 months after the surgery. A mixed-effects model was used for statistical analysis.

Results: Mean IOP significantly decreased from 14.7 ± 2.9 mmHg before surgery to 13.5 ± 2.9 mmHg (P = 0.002) at 1 month, 13.0 ± 2.4 mmHg (P < 0.0001) at 2 months, and 12.9 ± 2.8 mmHg (P < 0.0001) at 3 months after surgery. The mean corneal HOAs was 0.221 ± 0.136 μm preoperatively, and this was not significantly different compared with those postoperatively (0.208 ± 0.100 μm at 1 month, 0.222 ± 0.134 μm at 2 months, and 0.236 ± 0.176 μm at 3 months postoperatively). Similarly, the mean coma-like aberration (0.205 ± 0.132 μm) and the mean spherical-like aberration (0.080 ± 0.043 μm) preoperatively did not significantly change postoperatively.

Conclusion: Following iStent inject W implantation IOP is reduced whereas, corneal HOAs remain stable for up to 3 months.

Purpose: To investigate the long-term efficacy of accelerated corneal cross-linking (CXL) with Belin ABCD progression display in pediatric keratoconus patients.

Study design: Retrospective observational cohort study.

Methods: This retrospective study included 40 eyes of 40 pediatric keratoconus patients who underwent accelerated CXL (10 min/9 mW/cm²) and were followed at least 60 months after CXL. Corrected distance visual acuity, keratometry (K), anterior elevation, posterior elevation, asphericity, corneal densitometry, Belin/Ambrósio enhanced ectasia display and ABCD progression display values ​were recorded at baseline and 12 and 60 months after CXL.

Results: Iimprovements in visual acuity, gauged by regression in anterior curvature, progression in posterior curvature and corneal thickness, were observed using the ABCD progression display at the end of the 60 months follow-up. Significant improvements in K1, K2, maximum keratometry, anterior elevation and anterior asphericity values and significant worsening in the posterior elevation values were observed with topographical parameters. Significant thinning in pachymetric indices was observed with Belin/Ambrósio enhanced ectasia display.

Conclusion: Accelerated CXL is efficient in pediatric keratoconus patients in halting the disease progression. Visual and keratometric stabilization continued over a long follow-up period of 60 months. Belin ectasia progression display may be very helpful in the longitudinal follow-up of pediatric keratoconus patients after CXL.

Purpose: Rapid diagnosis and initiation of treatment are essential to improve outcomes for optic neuritis. However, many patients suspected of having optic neuritis may have different underlying conditions. This study aimed to investigate the spectrum of diseases in patients referred with suspected optic neuritis and to identify clinical factors associated with confirmed optic neuritis.

Study design: Retrospective cohort study METHODS: This study retrospectively reviewed 255 cases referred to Kobe University Hospital with suspected optic neuritis between January 2016 and June 2024. Cases were excluded if patients had a history of optic neuritis, encephalitis, or myelitis, were referred from non-ophthalmology departments, or resided outside Hyogo Prefecture. Logistic regression analysis was conducted to identify factors significantly associated with confirmed optic neuritis.

Results: Of the 206 eligible cases, 89 (43.2%) were confirmed to have optic neuritis. Other major diagnoses included anterior ischemic optic neuropathy (18.4%), space-occupying lesions such as intracranial tumors (11.7%), and retinal diseases or uveitis (10.2%). Logistic regression analysis revealed significant associations between confirmed optic neuritis and younger age, the presence of central scotoma, eye pain, decreased visual acuity, reduced critical flicker fusion frequency, and a shorter interval between symptom onset and consultation.

Conclusion: Although 43.2% of suspected cases were confirmed as optic neuritis, a substantial proportion was attributed to other conditions requiring distinct diagnostic and therapeutic approaches. These findings emphasize the critical role of multidisciplinary collaboration and evidence-based protocols in managing patients with acute visual impairment.