Background: Little is known about genotype–phenotype correlations of RP1-associated retinal dystrophies in the Japanese population. We aimed to investigate the genetic spectrum of RP1 variants and provide a detailed description of the clinical findings in Japanese patients. Methods: In total, 607 patients with inherited retinal diseases were examined using whole-exome/whole-genome sequencing (WES/WGS). PCR-based screening for an Alu element insertion (c.4052_4053ins328/p.Tyr1352AlafsTer9) was performed in 18 patients with autosomal-recessive (AR)-retinitis pigmentosa (RP) or AR-cone dystrophy (COD)/cone-rod dystrophy (CORD), including seven patients with heterozygous RP1 variants identified by WES/WGS analysis, and 11 early onset AR-RP patients, in whom no pathogenic variant was identified. We clinically examined 25 patients (23 families) with pathogenic RP1 variants, including five patients (five families) with autosomal-dominant (AD)-RP, 13 patients (11 families) with AR-RP, and seven patients (seven families) with AR-COD/CORD. Results: We identified 18 pathogenic RP1 variants, including seven novel variants. Interestingly, the Alu element insertion was the most frequent variant (32.0%, 16/50 alleles). The clinical findings revealed that the age at onset and disease progression occurred significantly earlier and faster in AR-RP patients compared to AD-RP or AR-COD/CORD patients. Conclusions: Our results suggest a genotype–phenotype correlation between variant types/locations and phenotypes (AD-RP, AR-RP, and AR-COD/CORD), and the Alu element insertion was the most major variant in Japanese patients with RP1-associated retinal dystrophies.

Purpose: To evaluate the optical coherence tomography (OCT) findings of epiretinal membrane (ERM) and its three associated diseases: macular pseudohole (MPH), ERM-foveoschisis (ERM-FS), and lamellar macular hole (LMH). Methods: We retrospectively reviewed all eyes that underwent vitrectomy with a follow-up of at least 6 months. All eyes were classified into four groups, ERM, MPH, ERM-FS, and LMH based on spectral-domain (SD) OCT findings. Factors analyzed included preoperative and postoperative best-corrected visual acuity (BCVA), presence of inner and outer retinal cysts, epiretinal proliferation (EP), and ellipsoid zone (EZ) disruption, central fovea thickness (CFT), central retina thickness (CRT), and macular volume (MV). Results: After enrolling 720 eyes of 664 patients, eyes were classified into four groups: ERM (592 eyes), MPH (76 eyes), ERM-FS (63 eyes), and LMH (42 eyes). BCVA significantly improved in all groups. Although preoperative BCVA was not significantly different among the four groups, postoperative BCVA was significantly worse in LMH versus ERM (p < 0.001). Inner and outer retinal cysts were significantly more prevalent in ERM-FS versus ERM and the other three groups, respectively. EP was significantly more frequently observed in LMH versus the other three groups (p < 0.001). CFT and CRT were significantly higher in ERM versus the other three groups, and MV was significantly larger in ERM than in MPH and LMH (p < 0.05). Conclusion: ERM had a higher CFT and CRT, and a larger MV. The postoperative BCVA was worse in LMH versus ERM, while LMH had a higher frequency of EP.

Background/Objectives: To investigate and compare the clinical characteristics of epiretinal membrane (ERM) and associated diseases: macular pseudohole (MPH), ERM foveoschisis (ERM-FS), and lamellar macular hole (LMH). Methods: We retrospectively reviewed of all patients who underwent vitrectomy with at least 6 months follow-up, all eyes were classified into four groups: ERM, MPH, ERM-FS, and LMH. Age, gender, presence of glaucoma, preoperative spherical equivalent, axial length (AL), preoperative and postoperative best-corrected visual acuity (BCVA), metamorphopsia using M-CHARTS^®, and frequency of overlapping associated diseases were investigated. The association between pre- and postoperative BCVA and these clinical factors was analyzed. Results: After enrolling 718 eyes of 662 patients, eyes were classified as ERM (592 eyes), MPH (76 eyes), ERM-FS (63 eyes), and LMH (42 eyes). Overlapping cases included MPH+ERM-FS (17 eyes), ERM-FS+LMH (14 eyes), MPH+LMH (18 eyes), and MPH+ERM-FS+LMH (3 eyes). The AL was significantly longer (p < 0.05) in MPH, ERM-FS, and LMH versus ERM. In all groups, BCVA significantly improved after vitrectomy. Although preoperative BCVA was not significantly different among the four groups, postoperative BCVA was significantly worse for LMH versus ERM (p < 0.001). Preoperative metamorphopsia was significantly more severe in ERM (0.52 ± 0.51) versus MPH (0.34 ± 0.29) (p < 0.05). Postoperative BCVA correlated with preoperative BCVA and age in all groups except LMH. Conclusions: Associated diseases often overlap and were more myopic than ERM. Postoperative BCVA was worse in LMH, while preoperative metamorphopsia was severe in ERM. These results highlight the importance of both clinical and functional evaluations in determining surgical indications and predicting visual outcomes.

To evaluate clinical and optical coherence tomography (OCT) findings and visual outcomes in patients with macular pseudohole (MPH), epiretinal membrane foveoschisis (ERM-FS), and lamellar macular hole (LMH) based on axial length (AL). We retrospectively reviewed consecutive patients diagnosed with MPH, ERM-FS, and LMH who underwent vitrectomy and were followed for at least 6 months postoperatively. In each disease group, eyes were categorized into three groups based on AL; normal (< 24 mm), myopic (≥ 24 to < 26 mm), and highly myopic (≥ 26 mm). Analyzed factors included age, AL, preoperative and postoperative best-corrected visual acuity (BCVA), and OCT parameters such as the presence of inner and outer retinal cysts, epiretinal proliferation, and ellipsoid zone disruption. A total of 171 eyes from 170 patients (79 males and 91 females) were included: 74 eyes with MPH, 59 eyes with ERM-FS, and 38 eyes with LMH. Postoperative BCVA significantly improved in all AL groups across all disease types. In the MPH group, postoperative BCVA was significantly better in the highly myopic group than in the myopic group (p = 0.04). There were no significant differences in the frequency of the OCT findings among the AL groups in any of the diseases. However, the presence of outer cysts at 6 months postoperatively tended to be more frequent in the highly myopic group in LMH (p = 0.065). Vitrectomy improved visual acuity in all AL groups across MPH, ERM-FS, and LMH. AL did not significantly affect the frequency of abnormal findings for the preoperative and postoperative OCT.

This study aimed to evaluate the changes in visual outcomes and optical coherence tomography (OCT) findings in patients with lamellar macular hole (LMH) following vitrectomy. Consecutive patients diagnosed with LMH based on OCT findings who underwent vitrectomy between April 2020 and December 2023 were included. Forty-two patients (male, n = 21; female, n = 21; mean age, 71.3 ± 8.2 years) were included in the study. Preoperative and postoperative best-corrected visual acuity (BCVA) and OCT parameters, including the presence of inner and outer retinal cysts, epiretinal proliferation (EP), and ellipsoid zone disruption (EZ), were analyzed. Postoperative BCVA was assessed at 6 months after surgery, and postoperative OCT findings were evaluated at 1, 3, and 6 months using all available data. Mean BCVA significantly improved from 0.36 ± 0.33 logarithm of the minimal angle of resolution preoperatively to 0.15 ± 0.26 at 6 months postoperatively (p < 0.001). The frequency of eyes with inner retinal cysts was 21.4% preoperatively, which gradually decreased to 8.0% at 6 months postoperatively. The frequency of outer retinal cysts was 54.8% preoperatively, which significantly decreased to 12.0% at 6 months postoperatively (p = 0.00937). The presence of EP was significantly correlated with worse postoperative BCVA (p < 0.05). Both preoperative and postoperative EZ disruptions significantly correlated with worse postoperative BCVA (p < 0.05). Vitrectomy for LMH improves visual acuity and reduces most intraretinal cysts within 6 months. EP, EZ disruption, and poor preoperative visual acuity were identified as factors associated with poor visual outcomes in patients with LMH.

Anatomic restoration after vitrectomy for lamellar macular hole (LMH) is not always achieved. However, the impact of unresolved LMH on visual outcomes remains unclear. We evaluated postoperative outcomes in eyes with unresolved LMH and postoperative full-thickness macular hole (FTMH) to reassess the meaning of anatomic success after LMH surgery. Multicenter, retrospective cohort study. One hundred sixty-six consecutive eyes of 166 patients who underwent vitrectomy for LMH. Anatomic success was defined as restoration of foveal configuration, whereby the postoperative OCT findings no longer met the diagnostic criteria for LMH. Postoperative anatomic outcomes were classified as anatomic success, unresolved LMH (including both persistent or recurrent LMH), or postoperative FTMH. Incidence and risk factors of unresolved LMH and postoperative FTMH, and best-corrected visual acuity (BCVA). Anatomic success was achieved in 141 eyes (84.9%), whereas 14 eyes (8.4%) had unresolved LMH and 11 eyes (6.6%) progressed to FTMH during follow-up (mean 17.8 months). At 12 months, BCVA was significantly worse in eyes with unresolved LMH than in those with anatomic success (0.24 ± 0.24 vs. 0.09 ± 0.19 logarithm of the minimum angle of resolution [logMAR]; P=0.041). Internal limiting membrane (ILM) peeling was significantly associated with a reduced risk of unresolved LMH (odds ratio [OR], 0.011; 95% CI, 0.002-0.062; P<0.001). Postoperative FTMH was significantly associated with epiretinal proliferation (P=0.018), thinner preoperative central foveal thickness (P=0.017), and no ILM peeling (P=0.001). Multivariable analysis confirmed that ILM peeling was an independent factor preventing postoperative FTMH (OR, 0.080; 95% CI, 0.010-0.620; P=0.001). Postoperative FTMH achieved closure in 9 eyes (82%) with additional treatment or observation, while the final BCVA was significantly worse in eyes that developed FTMH than in those with anatomic success (0.50 ± 0.32 vs. 0.12 ± 0.20 logMAR; P<0.001). While most eyes achieved anatomic success after vitrectomy for LMH, approximately 15% developed unresolved LMH or postoperative FTMH, both of which were associated with the absence of ILM peeling. Because anatomic failure was associated with poorer visual outcomes, foveal restoration on OCT may represent a more clinically meaningful anatomic endpoint after LMH surgery.