Japanese Journal of Ophthalmology最新文献

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.

Central serous chorioretinopathy (CSC) is a common disorder characterized by serous retinal detachment. Several studies using indocyanine green angiography (ICGA) have revealed that choroidal filling delay, choroidal vascular dilation, and choroidal vascular hyperpermeability are the characteristic findings of CSC. These ICGA findings confirm that choroidal circulatory disturbances are the primary factors in the pathogenesis of CSC. With advancements in optical coherence tomography (OCT), choroidal thickness has been found to be significantly greater in eyes with CSC than in normal eyes. Dilated large choroidal vessels reportedly account for the thickened choroid in eyes with CSC. Although many possible mechanisms and risk factors have been suggested, the pathophysiologic features of choroidal circulatory disturbances and choroidal thickening in eyes with CSC have not yet been fully elucidated. Recently, using anterior segment OCT, we proposed that the sclera may induce choroidal circulatory disturbances since CSC eyes have significantly thicker sclera than do normal eyes. This review summarizes updated information on the close relationship between CSC pathogenesis and the sclera.

Purpose: This study evaluated the role of shear wave elastography imaging (SWEΙ) in uveal melanomas and the associations between SWEI and clinical and hemodynamic findings.

Study design: Prospective, clinical study METHODS: Twelve patients with uveal melanomas, scheduled to undergo Ru-106 brachytherapy, were prospectively recruited from the Department of Ophthalmology of the University Hospital of Heraklion (September-December 2022). B-mode, hemodynamic and SWEI ultrasonography examinations were performed with the HiScan (OPTIKON 2000) and the LOGIQ E9 (GE Healthcare) sonographic systems, respectively. Differences in SWEI scores (kPa) between tumor (TS) and adjacent non-affected choroid (CS), as well as between TS and orbital fat (FS) were examined. Correlations between SWEI and intra-tumoral hemodynamic parameters, including peak systolic and end diastolic velocities and resistivity index (RI) were also examined.

Results: TS was significantly correlated with intra-tumoral RI (Pearson's bivariate correlation coefficient 0.681, p=0.015) and with maximal tumor height (Pearson's bivariate correlation coefficient 0.620, p=0.031). TS was significantly higher than both FS and CS scores (paired-samples t-test, p=0.003 and p=0.006, respectively).

Conclusions: SWEI score is applicable as a quantitative biomechanical marker in the assessment of choroidal melanoma. Choroidal melanomas are stiffer than both adjacent choroid and orbital fat. Moreover, choroidal melanomas with higher RI as well as those with higher apical elevations display higher SWEI scores.

Purpose: To assess the effects of 1% azithromycin ophthalmic solution (AZM) in patients with bacterial blepharitis accompanied by meibomian gland dysfunction (MGD).

Study design: A multicenter, single arm, prospective interventional study.

Methods: AZM was administered to the affected eyes twice daily for the first 2 days and once daily for the subsequent 12 days. Lid margin hyperaemia/redness, collarette at the root of the eyelashes, conjunctival hyperaemia, foreign body sensation, and epiphora were assessed on Days 1, 14, and 28. The Dry Eye-related Quality of Life Score (DEQS) and objectives related to MGD, including lid vascularity, lid margin irregularity, foaming, lid plugging, keratoconjunctival disorders, Marx line, meibum grade, and tear breakup time, were also assessed. Bacterial culture of the conjunctival sac and meibum was performed on Days 1 and 14.

Results: Twenty-four eyes of 24 patients (10 men/14 women, mean age 72.3 ± 13.2) were included. On Days 14 and 28, the total score, lid vascularity, lid plugging, and meibum grade showed significant improvement (p < 0.05). On Day 1, 71 strains were isolated from 22 of the 24 eyes (91.7%). Cutibacterium acnes, Corynebacterium spp., and Staphylococci were detected at high frequencies. The overall disappearance rates of the bacteria in the conjunctival sac and meibum at the end of treatment were 65.7% and 58.3%, respectively. No serious ocular or systemic adverse events were observed.

Conclusion: Fourteen-day treatment with AZM was effective in patients with blepharitis accompanied by MGD, and the efficacy of AZM persisted for a period after the treatment.

Purpose: To evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD).

Study design: Retrospective, interventional case series.

Methods: We retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8 mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined.

Results: BCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8 mg (all P < 0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss.

Conclusions: Intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis.