Japanese Journal of Ophthalmology最新文献

Purpose: To investigate the timing of enucleation, treatment course, and outcome for retinoblastoma (RB) with optic nerve (ON) invasion on imaging.

Study design: Retrospective clinical study.

Methods: Of the 160 patients with RB who presented to the National Center for Child Health and Development in Japan between 2005 and 2022, ON invasion on imaging at the initial presentation was seen in five patients. The clinical, computed tomography (CT), and magnetic resonance imaging (MRI) findings, and treatment courses were reviewed retrospectively.

Results: MRI showed ON invasion in all five patients (three with unilateral RB, 2 with bilateral RB); in two patients CT detected no invasion. Enucleation was performed in four patients, three of whom underwent neoadjuvant therapy and one had a positive ON resection margin following the enucleation as initial treatment. One patient did not undergo enucleation due to cerebrospinal fluid dissemination. All enucleated patients underwent adjuvant chemotherapy. Four patients underwent radiotherapy. During follow-up (mean, 89.4 months), four patients survived and one died.

Conclusion: MRI is recommended to evaluate ON invasion and determine the timing of enucleation for RB. The appropriate choice of neoadjuvant or adjuvant therapy would be helpful to avoid radiotherapy for RB with ON invasion on imaging.

Purpose: To assess the feasibility of swept-source optical coherence tomography angiography (SS-OCTA) to differentiate macular diseases, including nonpolypoidal macular neovascularization (MNV), polypoidal choroidal vasculopathy (PCV), type 3 MNV, and chronic central serous chorioretinopathy (CSC) without indocyanine green angiography (ICGA).

Study design: Retrospective observational study.

Methods: This study examined 63 eyes of 63 patients with treatment-naive neovascular age-related macular degeneration (AMD), including 23 eyes with nonpolypoidal MNV, 17 eyes with PCV, and 1 eye with type 3 MNV and 22 eyes with chronic CSC. Two independent retina specialists, blinded to the clinical diagnosis, assessed each case of neovascular AMD and chronic CSC using only B-scan and en face images of SS-OCTA without referring to other examination outcomes.

Results: By SS-OCTA alone, 19 eyes were diagnosed with nonpolypoidal MNV, 17 eyes with PCV, 2 eyes with type 3 MNV, and 22 eyes with chronic CSC, indicating high sensitivity (82.6%, 94.1%, 100%, and 100%, respectively) and specificity (100%, 97.8%, 98.4%, and 100%, respectively); however, three eyes could not be diagnosed because of obscure images. The agreement of diagnosis with SS-OCTA alone was high between the two specialists (κ = 0.82).

Conclusion: SS-OCTA showed high sensitivity and specificity in the differentiation of nonpolypoidal MNV, PCV, type 3 MNV, and chronic CSC. The differential criteria based on SS-OCTA could be a substitute for the ICGA-based diagnoses.

Purpose: There is limited evidence to evaluate the numerical cutoff point for detecting early presbyopia. Thus, we aimed to establish a clinically relevant optimal cutoff value of near visual acuity for detecting early presbyopia.

Study design: Prospective diagnostic accuracy study.

Methods: We included consecutive individuals aged ≥ 20 years with a binocular-corrected distance visual acuity of ≥ 20/25 who did not undergo ophthalmic surgery between December 17, 2020 and December 19, 2021, at two healthcare facilities in Japan. Binocular distance-corrected near visual acuity at 40 cm, accommodative amplitude, awareness of presbyopia, and Near Activity Visual Questionnaire scores were examined. The optimal cutoff values of distance-corrected near visual acuity for diagnosing early presbyopia were evaluated using receiver operating characteristic plots.

Results: Among 115 participants, 74 (64.3%) had presbyopia. The proportion of participants with no difficulty performing near-vision tasks decreased markedly when near visual acuity decreased to 20/20 (> 0.00 logMAR). A cutoff value of 0.00 logMAR for distance-corrected near visual acuity was optimal, showing high sensitivity of 56.76% and specificity of 92.68%, as opposed to the commonly used cutoff value of 0.40 logMAR (20/50; sensitivity, 9.46% and specificity, 100%) for diagnosing early presbyopia.

Conclusion: Near visual acuity of 0.00 logMAR (20/20) could be the optimal cutoff value for diagnosing early presbyopia.

Purpose: To evaluate the pharmacokinetics of ganciclovir eye drops by comparing solutions prepared from ganciclovir for intravenous infusion and ganciclovir gel and to assess the impact of systemic administration on drug levels in ocular tissues and serum.

Study design: Experimental study design.

Methods: Ganciclovir solutions (0.5% and 1.0%) prepared by diluting DENOSINE ^® IV Infusion in saline and 0.15% ganciclovir gel (Virgan^®) were topically administered in rabbit eyes, with and without concomitant systemic administration of ganciclovir. The concentrations of ganciclovir in the corneal epithelium, stroma, and endothelium, aqueous humor; and blood plasma were analyzed by high-performance liquid chromatography (HPLC).

Results: The ganciclovir solutions (0.5% and 1.0%) maintained therapeutic ganciclovir levels in the corneal endothelium above the effective dose required for 50% inhibition (ED50) up to 6 h, albeit with a swift decline thereafter. The 0.15% ganciclovir gel maintained higher therapeutic concentrations in the corneal endothelium for up to 12 h, exceeding the ED50. Serum concentrations of ganciclovir were significantly elevated in the groups receiving combined systemic administration.

Conclusion: Topical application of 0.15% ganciclovir gel maintained high endothelial concentrations, well above the therapeutic threshold, with or without systemic administration. Furthermore, the observed increase in ganciclovir levels within the plasma and aqueous humor following systemic administration posits it as a viable strategy for severe cases of cytomegalovirus corneal endotheliitis or those inadequately managed by local treatments alone.

Purpose: To compare the cleanliness of the conjunctival sac following the use of iodine compounds (PAI) and levofloxacin as postoperative eye drops.

Study design: A prospective open-label study.

Patients and methods: Either topical levofloxacin or fourfold-diluted PAI was administered for 1 week postoperatively in 128 eyes of 128 patients who underwent routine cataract surgery. Conjunctival samples were obtained at three time points: pre-surgery, 1 week postoperatively, and 1 month postoperatively.

Results: The respective positive bacterial culture rates for postoperative iodine and levofloxacin were 88.1% and 85.2% pre-surgery, 71.6% and 50.8% 1 week postoperatively, and 92.5% and 86.5% 1 month postoperatively. Positive bacterial culture rates in both groups significantly declined at 1 week, and the rates returned to the baseline level 1 month postoperatively. The magnitude of reduction of DNA copy number detected by polymerase chain reaction at 1 week was larger in the levofloxacin group, although no significant differences were seen at pre-surgery or 1 month postoperatively. In the levofloxacin group, only one strain was culture positive at 1 week, however, its minimum inhibitory concentration (MIC) against S. epidermidis was high (128 µg/ml). The MIC value increased from 2.31 ± 2.19 µg/ml pre-surgery to 57.14 ± 22.34 µg/ml 1 month postoperatively, while no significant change was found in the iodine group.

Conclusion: Postoperative iodine and levofloxacin eye drops both reduced bacterial contamination in the conjunctival sac, with a superior level of disinfection in the levofloxacin group. However, postoperative levofloxacin eye drops enhanced the emergence of highly resistant bacteria, whereas no such development was seen in the iodine group.

Purpose: To explore the frequency and positions of genetic mutations in CYP1B1 and FOXC1 in a Japanese population.

Study design: Molecular genetic analysis.

Methods: Genomic DNA was extracted from 31 Japanese patients with childhood glaucoma (CG) from 29 families. We examined the CYP1B, FOXC1, and MYOC genes using Sanger sequencing and whole-exome sequencing (WES).

Results: For CYP1B1, we identified 9 families that harbored novel mutations, p.A202T, p.D274E, p.Q340*, and p.V420G; the remaining mutations had been previously reported. When mapped to the CYP1B1 protein structure, all mutations appeared to influence the enzymatic activity of CYP1B1 by provoking structural deformity. Five patients were homozygotes or compound heterozygotes, supporting the recessive inheritance of the CYP1B1 mutations in CG. In contrast, four patients were heterozygous for the CYP1B1 mutation, suggesting the presence of regulatory region mutations or strong modifiers. For the FOXC1 gene, we identified 3 novel mutations, p.Q23fs, p.Q70R, and p.E163*, all of which were identified in a heterozygous state. No mutation was found in the MYOC gene in these CG patients. All individuals with CYP1B1 and FOXC1 mutations were severely affected by early-onset CG. In the CYP1B1-, FOXC1-, and MYOC-negative families, we also searched for variants in the other candidate genes reported for CG through WES, but could not find any mutations in these genes.

Conclusions: Our analyses of 29 CG families revealed 9 families with point mutations in the CYP1B1 gene, and four of those patients appeared to be heterozygotes, suggesting the presence of complex pathogenic mechanisms. FOXC1 appears to be another major causal gene of CG, indicating that panel sequencing of CYP1B1 and FOXC1 will be useful for diagnosis of CG in Japanese individuals.

Purpose: To investigate the visual prognosis of ocular surface squamous neoplasia (OSSN) after tumor resection and ocular surface reconstruction, and clarify factors that influence recurrence.

Study design: Retrospective cohort study.

Methods: Medical records of all patients who underwent surgical treatment for OSSN at our hospital between January 1996 and December 2019 were reviewed. Tumor size/location, histological classification, surgical procedure, intraoperative mitomycin-C use, and postoperative topical 5-fluorouracil (5-FU) administration were examined, and pre and postoperative visual acuity (VA) were compared to elucidate factors that influence disease recurrence.

Results: Tumor excision was performed in 70 eyes of 70 cases (43 men, 27 women; average age: 71.6 ± 12.6 years) with dysplasia (8 eyes), carcinoma in situ (26 eyes), and invasive squamous cell carcinoma (36 eyes). Tumors were found in the limbus (N = 59 eyes), palpebral conjunctiva (N = 8 eyes), and from the bulbar to palpebral conjunctiva (N = 3 eyes). Surgical procedures performed were limbal transplantation/keratoepithelioplasty (N = 29 eyes), cultivated oral mucosal epithelial transplantation (N = 3 eyes), and auto-conjunctival epithelium transplantation (N = 2 eyes). Ocular surface was reconstructed using amniotic membrane, donor cornea, or cultivated epithelial sheet. The mean follow-up was 38.6 ± 38.6 months (range, 2 months to 13.8 years). VA postoperatively improved in 25 (61.0%) cases. Recurrence occurred in 19 (27.1%) cases at from 2 to 50 months (median: 12.5 months) postoperative. Uni- and multivariate analyses revealed that presurgical tumor size and postoperative administration of 5-FU were significantly related to recurrence.

Conclusion: Combined surgical excision and postoperative topical 5-FU administration effectively prevented OSSN recurrence, and ocular surface reconstruction contributed to improvement of VA.

In today’s globalized society, ophthalmologists can examine people of different ethnicities regardless of where they live. The frequency of disease-causing genes varies according to a patient’s ethnic background. We explain genetic findings for Japanese patients with inherited eye diseases. Ocular genetics has made great advances over the past 30 years. For example, detecting mutations at nucleotide position 11778 in mitochondrial DNA was useful in the genetic diagnosis of Leber’s hereditary optic neuropathy (LHON). I evaluated the genotype-phenotype relationship in cases of corneal dystrophy and inherited retinal dystrophy (IRD). I identified the entire exon sequence of the eyes shut homolog (EYS) gene in patients with autosomal recessive retinitis pigmentosa (RP). EYS gene mutations are the most frequent cause of autosomal recessive RP. RPGRIP1 may be a common causative gene with early-onset severe retinal dystrophy, including Leber congenital amaurosis. However, some genes have complex structures that are difficult to analyze, including the OPN1LW/OPN1MW gene cluster in blue cone monochromacy and the IKBKG/NEMO genes in incontinentia pigmenti. This review will also present two cases with uniparental disomy, a case of IRD with double mutations, and a case with RP complicated with LHON-like neuropathy. Precise understanding of the effects of genetic variants may reveal differences in the clinical characteristics of patients with the same variant. When starting genome medicine, accurately diagnosing the patient, making accurate prediction, determining the genetic pattern, and providing genetic counseling are important. Above all, that both the doctors and patients understand genetic diseases correctly is important.

Purpose

The high prevalence of allergic conjunctivitis in Japan necessitates novel, easy-to-use treatment options for prophylactic use. We evaluated the safety and efficacy of a newly-developed 0.5% epinastine topical eyelid cream to prevent the development of allergic conjunctivitis.

Study design

This was a phase 3, single-centre, double-masked, intra-patient randomised trial in asymptomatic adults (aged 20–65 years) with seasonal allergic conjunctivitis in Japan.

Methods

The left and right eyes of eligible patients were randomised to receive a topical application of either 0.5% epinastine cream (~ 30 mg per dose) to one eye or placebo cream to the other (on the outer skin of the upper and lower eyelids) after a conjunctival antigen challenge (CAC) test. Symptom severity was assessed up to 24 h post-treatment. Primary efficacy endpoints were mean ocular itching and conjunctival hyperaemia severity scores in each eye; safety endpoints included adverse events (AEs) and adverse drug reaction (ADRs).

Results

In total, 30 patients (60 eyes) were included in the study. The 0.5% epinastine topical eyelid cream reduced mean ocular itching scores (difference in least squares means ± standard error, − 1.12 ± 0.214; p < 0.0001) and mean conjunctival hyperaemia scores (− 0.54 ± 0.197; p = 0.0097) 24 h after treatment versus placebo. The 0.5% epinastine topical eyelid cream was well tolerated, with no AEs or ADRs reported.

Conclusion

With its novel route of administration, 0.5% epinastine topical eyelid cream may be considered a unique, easy-to-use, once-daily treatment option to prevent the onset of seasonal allergic conjunctivitis.

Purpose: To evaluate the clinical features and prognosis of conjunctival melanoma in Japanese patients.

Study design: Retrospective observational case series.

Methods: Twenty patients (8 men and 12 women) diagnosed with conjunctival melanoma at a singlehospital between 2003 and 2017 were analyzed. Data on clinical presentation, sex, age, the affected eye, tumor location, tumor origin, tumor stage according to the American Joint Committee on Cancer staging system (eighth edition), treatment, outcomes, local recurrence, metastasis, and survival were extracted from the patients' medical records and reviewed.

Results: The mean age at diagnosis was 64.2 ± 14.8 years. Tumor locations at the first examination included the bulbar conjunctiva (n = 19), plica (n = 13), and fornix (n = 12). The tumor stage was T1 in 5 cases (25%), T2 in 12 cases (60%), T3 in 3 cases (15%), and T4 in none. The mean follow-up duration was 91.7 ± 46.0 months. The local recurrence rates at 1, 5, and 10 years were 5.0%, 18.8%, and 31.5%, respectively, whilst the metastasis rates were 5.0%, 25.6%, and 32.4%, respectively. Four of the 6 patients who experienced metastasis died; duration from metastasis to death was 17.5 months (range, 7-25). The 5-year survival rate for conjunctival melanoma was 78.8%. Tumor thickness was significantly associated with survival duration on univariate Cox regression analyses.

Conclusion: The mortality rate for conjunctival melanoma in the Japanese population was lower and higher than that reported in the Chinese and United States populations, respectively. Tumor thickness was a prognostic factor for survival in patients with conjunctival melanoma.