Japanese Journal of Ophthalmology最新文献

Purpose: To reveal the penetration of epinastine, an anti-allergic ophthalmic agent, into the eyelid and its distribution to the conjunctiva after administration of a cream formulation on rabbit eyelid skin.

Study design: Experimental study.

Methods: Rabbits were treated with 0.5% epinastine cream on hair-shaved eyelids, followed by preparation of eyelid tissue slices to determine spatial tissue distribution of epinastine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification using laser-microdissected tissues and desorption electrospray ionization mass spectrometry imaging (DESI-MSI). In addition, following either eyelid application of 0.5% epinastine cream or ocular instillation of 0.1% epinastine eye drops, concentration-time profiles of epinastine in the palpebral conjunctiva and bulbar conjunctiva were determined using LC-MS/MS.

Results: Laser microdissection coupled with LC-MS/MS analysis detected high concentrations of epinastine around the outermost layer of the eyelid at 0.5 h post-administration that gradually diffused deeper into the eyelid and was distributed in the conjunctival layer at 8 and 24 h post-administration. Similar time-dependent drug distribution was observed in high-spatial-resolution images obtained using DESI-MSI. Epinastine concentrations in the conjunctival tissues peaked at 4-8 h after administration of 0.5% epinastine cream and then decreased slowly over 72 h post-administration. In contrast, epinastine concentrations peaked quickly and decreased sharply after epinastine eye drop administration.

Conclusion: After the application of epinastine cream to the eyelid skin, epinastine gradually permeated the eyelid. The compound was retained in the conjunctiva for 8-24 h post-administration, indicating that epinastine cream is a promising long-acting formulation for treating allergic conjunctivitis.

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP).

Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial.

Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated.

Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group.

Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.

Purpose: To investigate the surgical outcomes of intrascleral intraocular lens (IOL) fixation using a modified extraocular forceps-guided technique.

Study design: Retrospective case series.

Methods: Overall, 81 eyes of 78 patients who underwent intrascleral IOL fixation using the modified extraocular forceps-guided technique were included. The procedure entailed creating 2 scleral half-layer T-shaped incisions perpendicular to the main incision and forming a scleral tunnel. A 25-gauge trocar was inserted at the lower end of the T-shaped incision to perform vitrectomy. A 27-gauge needle was inserted from the left-hand port, and the leading haptic was inserted into the needle lumen. After removal of the right-hand trocar, a 90°-curved intrascleral fixation forceps was inserted into the eye, exposing the tip at the main incision, thus allowing the tip of the extraocular trailing haptic to be gripped and both haptics to be pulled out. The left-hand trocar was removed, and the haptics were buried in the scleral tunnel. The surgical outcomes of this technique were retrospectively evaluated on the basis of the medical records.

Results: The induction of haptics was successful in all cases. The preoperative best-corrected visual acuity improved from 0.35±0.68 to 0.12±0.36 logMAR postoperatively (P<0.01). The refractive error was -0.27±0.87 D; IOL decentration, 0.39±0.18 mm; IOL tilt, 5.97±2.65°; IOL astigmatism, 0.35±0.36 D; and corneal endothelial cell loss, 10.3±12.7%. There were no serious complications related to the surgical technique.

Conclusion: The modified extraocular forceps-guided technique allows for safe and straightforward induction of the trailing haptics and enables the performance of intrascleral IOL fixation with minimal scleral incisions.

Purpose: To evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup.

Study design: YOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 faricimab trials.

Methods: Patients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891).

Results: In the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92-100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept.

Conclusion: Faricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort.

Purpose: To assess the effectiveness of switching from the concomitant use of brinzolamide 1% (BZM) and brimonidine 0.1% (BMD) to a BZM/BMD fixed-dose combination (BBFC) for the reduction of corneal epithelial damage.

Study design: Retrospective cohort study.

Methods: This study involved 52 eyes of 52 glaucoma patients (26 women, 26 men; mean age: 67.0 ± 14.0 years) followed for more than 3 months after being switched from concomitant BZM and BMD to BBFC. Superficial punctate keratitis (SPK) was assessed by fluorescein staining according to the National Eye Institute classification, with the cornea divided into 5 areas: center, superior, nasal, temporal, and inferior. SPK density was graded as 0 (no SPK), 1 (separate SPK), 2 (moderately dense SPK), and 3 (high SPK with overlapping lesions). SPK scores and intraocular pressure (IOP) at pre switching to BBFC (pre-BBFC) and at 3-months post switching to BBFC (post-BBFC) were then compared using the Wilcoxon signed-rank test.

Results: At pre-BBFC and post-BBFC, respectively, mean IOP was 12.4 ± 2.5 and 12.4 ± 2.7 mmHg, thus illustrating no significant difference in IOP between pre and post switch (p = 0.924), and the mean SPK score for center, superior, nasal, temporal, and inferior was 0.06 ± 0.24, 0.04 ± 0.19, 0.52 ± 0.67, 0.15 ± 0.36, and 0.92 ± 0.74, and 0.04 ± 0.19, 0.02 ± 0.14, 0.37 ± 0.56, 0.04 ± 0.19, and 0.75 ± 0.62, thus clearly showing a significant reduction in SPK scores for the nasal, temporal, and inferior areas at post-BBFC compared to those at pre-BBFC (p < 0.05).

Conclusion: Our findings reveal that compared with the concomitant use of BZM and BMD, BBFC is effective in reducing corneal epithelial damage.

Purpose: To investigate the visual prognosis of metamorphopsia in patients undergoing surgery for stage 3 idiopathic epiretinal membrane (ERM) by Govetto classification using preoperative optical coherence tomography (OCT) parameters.

Study design: Retrospective clinical study.

Method: This study included 45 eyes of 45 patients with a minimum follow-up period of 3 months. The best-corrected visual acuity (BCVA) and metamorphopsia score using the M-CHARTS were recorded. Central foveal thickness (CFT), inner nuclear layer thickness (INL), ectopic inner retinal layer thickness (EIFL), outer retinal layer thickness, disruption of the ellipsoid zone, cotton ball sign, and intraretinal cystoid changes were measured based on spectral domain OCT. Preoperative and postoperative values and conditions were compared, and correlations between the preoperative values or conditions and postoperative metamorphopsia scores or BCVA were analyzed.

Results: After surgery, the horizontal, vertical, and mean metamorphopsia scores, as well as BCVA, CFT, INL, and EIFL significantly improved (p < 0.001). Using multivariate analysis, only preoperative CFT was a significant explanatory parameter for both the postoperative horizontal metamorphopsia scores and mean values of the postoperative horizontal and vertical metamorphopsia scores (p = 0.019 and p = 0.011, respectively). Age (p = 0.011) and preoperative CFT (p = 0.026) were significant explanatory parameters of postoperative BCVA.

Conclusion: Preoperative CFT significantly correlated with postoperative metamorphopsia in patients undergoing surgery for stage 3 idiopathic ERM. This finding might help surgeons predict postoperative visual outcomes and make timely surgical decisions.

Purpose: To compare the distance of the medial rectus muscle insertion to the limbus (DMIL) between patients with acute acquired comitant esotropia (AACE) associated with excessive digital device usage (EDDU) and exotropic patients.

Study design: Retrospective study.

Methods: The medical records of 72 eyes of 44 patients with EDDU were retrospectively analyzed. The DMIL was measured from the anterior part at the midpoint of the medial rectus muscle insertion into the anterior limbus using a caliper after dissecting the medial rectus muscle with two control sutures at 12 o'clock and 6 o'clock. The DMIL in the non-fixation eye was compared between 44 patients with AACE and 23 patients with exotropia.

Results: The mean daily EDDU was 6.5 ± 3.1 h. The mean cycloplegic refractive errors (spherical equivalent: SE) were - 3.18 ± 2.52 diopters (D) OD and - 3.03 ± 2.42 D OS. The mean DMIL in the 72 eyes of 44 patients with AACE associated with EDDU was 4.30 ± 0.66 mm. The difference in DMIL of non-fixation eyes between 44 AACE patients and 23 exotropic patients was significant (4.28 ± 0.65 mm vs. 5.28 ± 0.50 mm, p < 0.0001). However, the SE in 44 non-dominant eyes of AACE was - 3.08 ± 2.56 D, significantly stronger than - 1.22 ± 1.93 D in the 23 exotropic eyes (p = 0.008).

Conclusion: DMIL in patients with AACE associated with EDDU was significantly shorter. This anatomical anomaly may be an etiology of AACE associated with EDDU.

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 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.