Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients\' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

UNASSIGNED: To delineate the natural history of visual function parameters over time in individuals with Bietti crystalline dystrophy.
UNASSIGNED: This was a single-center retrospective longitudinal cohort study. Participants (n = 29) with a clinical diagnosis of Bietti crystalline dystrophy who harbored two alleles of disease-causing variants of the cytochrome P450 family 4 subfamily V member 2 gene (CYP4V2) were enrolled. Best-corrected visual acuity (BCVA), visual field (VF), and full-field ERG (ffERG) at baseline and their changes during the follow-up period were evaluated. Annual progression rates were calculated using three methods.
UNASSIGNED: The mean age at the initial visit was 34.2 ± 7.5 years, with 5.9 ± 3.1 years follow-up. The annual progression rate from the longitudinal analysis using averaged individual progression rates was 0.079 logMAR units for BCVA, 1.14 dB for mean defect (MD) value of VF, and -18.06 µV and -5.45 µV for the b-wave amplitudes of scotopic 3.0 ERG and photopic 3.0 ERG, respectively. Mixed-model linear regression revealed annual progression rates of 0.068 logMAR units, 0.86 dB, -13.29 µV, and -3.75 µV, respectively. Cross-sectional progression rates from visual function versus age at baseline were 0.011 logMAR units, 0.47 dB, -1.85 µV, and -1.07 µV, respectively, which were significantly slower than those from the longitudinal data. Interocular symmetries for the MD values of VF and ffERG were good.
UNASSIGNED: Annual BCVA, VF, and ffERG progression rates were rapid, emphasizing the need for regular follow-up and early intervention. The progression rate cannot be inferred accurately from cross-sectional data from patients of different ages.

OBJECTIVE: To evaluate the effectiveness of sequential custom phototherapeutic keratectomy (SCTK) for granular corneal dystrophy type 1 (GCD1).
METHODS: Thirty-seven eyes of 21 patients with GCD1 were treated with SCTK to remove superficial opacifications, regularize the corneal surface, and decrease optical aberrations. SCTK is a sequence of custom therapeutic excimer laser keratectomies with step-by-step intraoperative corneal topography monitoring of results. Six eyes of 5 patients previously treated with penetrating keratoplasty received SCTK for disease recurrence. Pre-operative and postoperative corrected distance visual acuity (CDVA), refractive values, mean pupillary keratometry, and pachymetry were retrospectively analyzed. The mean follow-up period was 41.3 months.
RESULTS: SCTK provided significant decimal CDVA improvement, from 0.33 ± 0.22 to 0.63 ± 0.24 (P < .0001) at the last available follow-up visit. One eye, initially treated with penetrating keratoplasty, showed visually significant disease 8 years after the first SCTK and was re-treated. Mean corneal pachymetry difference between preoperative and final follow-up values was 78.42 ± 62.26 µm. Mean corneal curvature and the spherical component did not show a statistically significant change or hyperopic shift. Astigmatism and higher order aberration reduction were statistically significant.
CONCLUSIONS: SCTK is a powerful tool for the treatment of anterior corneal pathologies hindering vision and quality of life, such as GCD1. SCTK is less invasive and fosters more rapid visual recovery than penetrating keratoplasty or deep anterior lamellar keratoplasty. Providing significant visual improvement, SCTK can be the preferred initial treatment in eyes with GCD1. [J Refract Surg. 2023;39(6):422-429.].

Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort.
Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively).
Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.

We determined the efficacy and safety of 0.1% RGN-259 ophthalmic solution (containing the regenerative protein thymosin ß4) in promoting the healing of persistent epithelial defects in patients with Stages 2 and 3 neurotrophic keratopathy. Complete healing occurred after 4 weeks in 6 of the 10 RGN-259-treated subjects and in 1 of the 8 placebo-treated subjects (p = 0.0656), indicating a strong efficacy trend. Additional efficacy was seen in the significant healing (p = 0.0359) with no recurrent defects observed at day 43, two weeks after cessation of treatment, while the one healed placebo-treated subject at day 28 suffered a recurrence at day 43. The Mackie classification disease stage improved in the RGN-259-treated group at Days 29, 36, and 43 (p = 0.0818, 0.0625, and 0.0467, respectively). Time to complete healing also showed a trend towards efficacy (p = 0.0829, Kaplan-Meier) with 0.1% RGN-259. RGN-259-treated subjects had significant improvements at multiple time points in ocular discomfort, foreign body sensation, and dryness which were not seen in the placebo group. No significant adverse effects were observed. In summary, the use of 0.1% RGN-259 promotes rapid healing of epithelial defects in neurotrophic keratopathy, improves ocular comfort, and is safe for treating this challenging population of patients.

To investigate the association of comorbidities including hyperparathyroidism and sociodemographic factors with band keratopathy.
This retrospective, population-based, matched case-control study recruited 2,545 patients suffering from band keratopathy. They were selected from the Taiwan National Health Insurance Research Database, based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 371.43. The control group included 15,270 sex-, age-, and index date-matched non-band keratopathy patients collected from the Taiwan Longitudinal Health Insurance Database 2000. To compare band keratopathy patients with controls, McNemar\'s test was used for nominal data and paired t- tests were used for continuous variables. Univariate conditional logistic regression analysis and multivariable conditional logistic regression were used to obtain the odds ratio (OR) and adjusted OR of developing band keratopathy.
Patients with hyperparathyroidism were more likely to develop band keratopathy than controls (OR, 43.5; 95% confidence interval [CI], 23.789-79.544; P < 0.001) even after conditional logistic regression (adjusted OR, 11.28; 95% CI, 5.461-23.33; P < 0.001). Other conditions that increased the odds of scleritis development included systemic diseases such as chronic kidney disease (CKD) and diabetes mellitus (DM) and ocular conditions such as iridocyclitis, phthisis bulbi, and ever silicone oil retention. Regarding sociodemographic factors, >40% of patients with band keratopathy were aged ≥65 years old. Moreover, patients living in Eastern Taiwan and fishermen had higher odds of developing band keratopathy.
Band keratopathy is significantly associated with hyperparathyroidism, CKD, DM, iridocyclitis, phthisis bulbi, and ever silicone oil retention.

To describe the clinical profile and demographic distribution of band-shaped keratopathy (BSK) in patients presenting to a multitier ophthalmology hospital network in India.
This cross-sectional hospital-based study included 2,664,906 new patients presenting between January 2011 and January 2021 (10-year period). Patients with a clinical diagnosis of BSK in at least one eye were included as cases. The data were collected using an electronic medical record system.
Overall, 8801 (0.33%) patients were diagnosed with BSK. The prevalence rates were 0.47% in children (age: <16 years) and 0.31% in adults. The majority of patients were males (62.87%) with unilateral affliction (85.21%). The mean age of the patients was 40.43 ± 23.14 years. The majority (16.93%) of the patients were in the age bracket of 11-20 years. A larger proportion of the patients were from higher socioeconomic status (60.46%) and the urban region (45.9%). Of the 10,103 eyes affected with BSK, the common ocular comorbidities were status post-vitreoretinal surgery (20.55%) and uveitis (12.7%) in children and corneal scar (41.23%) and spheroidal degeneration (13.7%) in adults. Most of the eyes had mild or no visual impairment (24.74%). Among the eyes that needed surgical intervention, chelation with ethylenediaminetetraacetic acid (EDTA) was the most performed surgical procedure (1.68%) along with phototherapeutic keratectomy (0.32%).
BSK commonly affects adult males and is unilateral in nature. The majority of the patients in this cohort belonged to higher socioeconomic strata and urban geography. At initial presentation, visual impairment was mild to moderate in a vast majority of the patients, and the most common surgical intervention performed was chelation with EDTA during the study period.

To investigate the association of recurrent corneal erosion (RCE) with sociodemographic factors and associated ocular conditions or systemic diseases.
This nationwide, population-based, retrospective, matched case-controlled study included 98,895 RCE patients, identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 371.42, were selected from the Taiwan National Health Insurance Research Database. The age-, sex-, and index date- matched control group included 98,895 non-RCE control group also selected from the Taiwan Longitudinal Health Insurance Database 2000. Sociodemographic factors and associated ocular conditions or systemic diseases were examined using univariate logistic regression analyses, and continuous variables were analyzed using paired t-test. The odds ratio (OR) of developing RCE were compared using adjusted logistic regression analysis.
Patients with ocular conditions including corneal abrasion, ocular allergic conditions, and corneal dystrophy were more likely to have RCE than the control group (adjusted OR = 63.56, 95% CI = 42.06-96.06, p < 0.0001; adjusted OR = 24.27, 95% CI = 20.51-28.72, p < 0.0001; adjusted OR = 17.10, 95% CI = 5.14-59.93, p < 0.0001, respectively). Patients with systemic diseases such as diabetes mellitus, hyperlipidaemia, and atopy trait have significantly higher ORs for RCE development. Patients residing in either Northern Taiwan or a metropolis city had higher odds of developing RCE; however, there were no significant differences in income or occupation on the probability to develop RCE.
RCE is strongly associated with corneal abrasion, ocular allergic conditions, corneal dystrophy, diabetes mellitus, hyperlipidaemia, and atopy trait.

OBJECTIVE: The purpose of this study was to evaluate the incidence and epidemiology of recurrent corneal erosion within a clinical population using standard diagnostic techniques and a new technique called the corneal sweep test (CST).
METHODS: A retrospective chart review was conducted on 58 eyes of 51 patients with the diagnosis of recurrent corneal erosion from July 2018 to June 2020. All underwent a thorough history and physical examination. The CST was performed as a confirmatory test and on any patient who lacked visible corneal pathology.
RESULTS: The CST was necessary on 49 of the 58 eyes to help confirm the diagnosis of a corneal erosion. Among them, 34 had an occult corneal erosion, which is defined as having a normal-appearing cornea on slitlamp examination but found to have loose corneal epithelium with the CST. Clear corneal cataract surgery (28 eyes, 48.2%) was the most common presumed mechanism of injury, with 20 (71.4%) developing symptoms only after cataract surgery. All 20 eyes had an erosion located directly over a clear corneal cataract incision.
CONCLUSIONS: The CST is a new and effective technique to help diagnose corneal erosions in the absence of visible corneal findings. Clear corneal cataract surgery is an under-recognized but important risk factor to consider because the incision can be the source for an erosion. Using the CST could lead to a paradigm shift in the way clinicians approach RCEs and patients with a persistent ocular pain syndrome.

OBJECTIVE: To evaluate recurrence and visual outcomes of phototherapeutic keratectomy (PTK) in lattice corneal dystrophy.
METHODS: Kaplan-Meier survival analyses were retrospectively performed. Recurrence was defined as central biomicroscopic findings of recurrence with decreased visual acuity: loss of at least two lines or visual acuity ≤ 20/40) at any time during the follow-up.
RESULTS: Twenty-two virgin eyes and 10 with previous keratoplasty (20 patients; 13 women and 7 men) were studied during a mean of 4.7 ± 3.5 years (range: 11 months to 18 years). One and 5 years after the first PTK (PTK1), 1 of 32 and 12 of 32 eyes, respectively, recurred. The cumulative probabilities of recurrence were 3%, 48%, and 89% in the whole sample at 1, 5, and 10 years, respectively. All cases in the virgin group and 8 eyes in the previous keratoplasty group improved their visual acuity. There were no significant differences in recurrence probability between groups (log-rank test; P = .86). A second PTK (PTK2) was performed in 15 of 32 eyes, with 6 postoperative recurrences recorded. The cumulative probabilities of recurrence in the whole sample were 18%, 30%, and 44% at 1, 3, and 5 years, respectively. Visual acuity improved in 11 of 13 eyes in the virgin group and 2 of 2 eyes in the previous keratoplasty group. Recurrence probability after PTK1 and PTK2 was similar in the whole sample (log-rank test; P = .637). Persistent graft edema after PTK1 in one eye was the only complication found.
CONCLUSIONS: PTK can be an effective, safe, and repeatable treatment to delay keratoplasty in symptomatic lattice corneal dystrophy. [J Refract Surg. 2022;38(1):43-49.].