Nationwide Prevalence of Inherited Retinal Diseases in the Israeli Population.

Importance: Data regarding the prevalence of various inherited retinal diseases (IRDs) are limited and vary across populations; moreover, nationwide prevalence studies may be limited to a specific IRD phenotype, potentially leading to inaccurate prevalence estimations. Therefore, nationwide prevalence data are needed. Objective: To determine the prevalence of 67 IRD phenotypes in the Israeli population. Design, Setting, and Participants: This cohort study collected nationwide data regarding the number of individuals affected with IRD phenotypes assessed in 10 clinical and academic centers in Israel as part of the research activity of the Israeli inherited retinal disease consortium. Data were collected in May 2023 on 9396 individuals residing in Israel who were diagnosed by an ophthalmologist with an IRD using either electroretinography or retinal imaging where included. Individuals with retinal diseases known to have a nonmendelian basis or without a clear genetic basis and those who were reported as deceased at the time of data collection were excluded from this study. Main Outcomes and Measures: Prevalence of 67 IRD phenotypes. Results: Among the 9396 participants in our cohort, the most common IRD in Israel was retinitis pigmentosa with a disease prevalence of approximately 1:2400 individuals, followed by cone-rod dystrophy (approximately 1:14 000), Stargardt disease (approximately 1:16 000), Usher syndrome (approximately 1:16,000), and congenital stationary night blindness (approximately 1:18 000). The prevalence of all IRDs combined was 1:1043 individuals. Conclusions and Relevance: The current study provides large prevalence dataset of 67 IRD phenotypes, some of which are extremely rare, with only a single identified case. This analysis highlights the potential importance of performing additional nationwide prevalence studies to potentially assist with determining the prevalence of IRDs worldwide.

Optical coherence tomography Angio-B mode for early detection of myopic choroidal neovascularization and treatment with Bevacizumab.

Purpose: The purpose of this case report is to outline the management of a 41-year-old female with pathological myopia and type II choroidal neovascularization (CNV) diagnosed by optical coherence tomography angiography (OCT-A) angio-B mode. Observations: The early detection of CNV with OCT-A angio-B mode and treatment with intra-vitreous injections of Bevacizumab contributed to the amelioration of her vision to 20/20, a better visual acuity than she had prior to treatment. Conclusions and importance: This case report suggests that an OCT-A scan may reveal the initial formation of abnormal vasculature before pathological changes are evident in structural OCT, allowing for prompt treatment and resolution in patients with myopic CNV.

Best Disease: Global Mutations Review, Genotype-Phenotype Correlation, and Prevalence Analysis in the Israeli Population.

Purpose: To review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population. Methods: Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources. Results: A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein. Conclusions: This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.

Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.

Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry. Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing). Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4. Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4-c.6077delT, is likely a founder mutation among the studied population. Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future.

A Novel Device for Suprachoroidal Drug Delivery to Retina: Evaluation in Nonhuman Primates.

Purpose: Evaluation of distribution and tolerance of suprachoroidal injection of indocyanine green (ICG) in nonhuman primates (NHPs) using a novel suprachoroidal (SC) delivery technology. Methods: Three live and three euthanized African green monkeys were injected with 150 or 200 µL ICG/eye into the SC space of both eyes, 2.5 mm posterior to the limbus in the inferior quadrant, utilizing a novel SC injector. Eyes were analyzed by imaging of scleral flatmounts. Live animals were observed for 24 hours for general health. Ophthalmic evaluation included slit-lamp biomicroscopy, tonometry, fundus imaging, confocal laser ophthalmoscopy, and spectral-domain optical coherence tomography (SD-OCT) before and at 10 minutes and 1, 3, and 24 hours post-injection. Results: SC dosing was successfully performed in all eyes. Infrared fundus imaging demonstrated ICG distribution throughout the posterior segment, reaching the macula within 24 hours post-injection. No inflammation, intravitreal penetration, SC blebs, retinal detachment, or hemorrhages were detected. No significant changes were observed in retinal thickness by SD-OCT (P = 0.267, ANOVA). A mild, statistically insignificant elevation in intraocular pressure was observed within 10 minutes post-injection (mean ± standard error: 7.28 ± 5.09 mmHg; P = 0.061) and was spontaneously resolved within the first hour after dosing. Conclusions: Suprachoroidal injection of 150 to 200 µL ICG dye was successfully performed and well tolerated in NHP eyes, with rapid distribution into the macular region and throughout the posterior pole. Translational Relevance: This novel SC drug delivery system may potentially provide safe and effective delivery of therapeutics to the posterior pole region in humans.

PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially modulated by inhibiting the thrombin cellular protease-activated receptor 1 (PAR1). Our aim was to study whether coagulation pathway modulation affects DE. Diabetic C57BL/6 mice were treated with PARIN5, a novel PAR1 modulator. Behavioral changes in the open field and novel object recognition tests, serum neurofilament (NfL) levels and thrombin activity in central and peripheral nervous system tissue (CNS and PNS, respectively), brain mRNA expression of tumor necrosis factor α (TNF-α), Factor X (FX), prothrombin, and PAR1 were assessed. Subtle behavioral changes were detected in diabetic mice. These were accompanied by an increase in serum NfL, an increase in central and peripheral neural tissue thrombin activity, and TNF-α, FX, and prothrombin brain intrinsic mRNA expression. Systemic treatment with PARIN5 prevented the appearance of behavioral changes, normalized serum NfL and prevented the increase in peripheral but not central thrombin activity. PARIN5 treatment prevented the elevation of both TNF-α and FX but significantly elevated prothrombin expression. PARIN5 treatment prevents behavioral and neural damage in the DE model, suggesting it for future clinical research.

Functional Carbon Quantum Dots for Ocular Imaging and Therapeutic Applications.

Carbon quantum dots (CDs) are a class of emerging carbonaceous nanomaterials that have received considerable attention due to their excellent fluorescent properties, extremely small size, ability to penetrate cells and tissues, ease of synthesis, surface modification, low cytotoxicity, and superior water dispersion. In light of these properties, CDs are extensively investigated as candidates for bioimaging probes, efficient drug carriers, and disease diagnostics. Functionalized CDs represent a promising therapeutic candidate for ocular diseases. Here, this work reviews the potential use of functionalized CDs in the diagnosis and treatment of eye-related diseases, including the treatment of macular and anterior segment diseases, as well as targeting Aß amyloids in the retina.

Machine learning for comprehensive prediction of high risk for Alzheimer's disease based on chromatic pupilloperimetry.

Currently there are no reliable biomarkers for early detection of Alzheimer's disease (AD) at the preclinical stage. This study assessed the pupil light reflex (PLR) for focal red and blue light stimuli in central and peripheral retina in 125 cognitively normal middle age subjects (45-71 years old) at high risk for AD due to a family history of the disease (FH+), and 61 age-similar subjects with no family history of AD (FH-) using Chromatic Pupilloperimetry coupled with Machine Learning (ML). All subjects had normal ophthalmic assessment, and normal retinal and optic nerve thickness by optical coherence tomography. No significant differences were observed between groups in cognitive function and volumetric brain MRI. Chromatic pupilloperimetry-based ML models were highly discriminative in differentiating subjects with and without AD family history, using transient PLR for focal red (primarily cone-mediated), and dim blue (primarily rod-mediated) light stimuli. Features associated with transient pupil response latency (PRL) achieved Area Under the Curve Receiver Operating Characteristic (AUC-ROC) of 0.90 ± 0.051 (left-eye) and 0.87 ± 0.048 (right-eye). Parameters associated with the contraction arm of the rod and cone-mediated PLR were more discriminative compared to parameters associated with the relaxation arm and melanopsin-mediated PLR. Significantly shorter PRL for dim blue light was measured in the FH+ group in two test targets in the temporal visual field in right eye that had highest relative weight in the ML algorithm (mean ± standard error, SE 0.449 s ± 0.007 s vs. 0.478 s ± 0.010 s, p = 0.038). Taken together our study suggests that subtle focal changes in pupil contraction latency may be detected in subjects at high risk to develop AD, decades before the onset of AD clinical symptoms. The dendrites of melanopsin containing retinal ganglion cells may be affected very early at the preclinical stages of AD.

THE TARGET SIGN: A Near Infrared Feature and Multimodal Imaging in a Pluri-Ethnic Cohort with RDH5-Related Fundus Albipunctatus.

PURPOSE: Retinol dehydrogenase 5 (RDH5)-related fundus albipunctatus can present with phenotypic variability. Our purpose was to investigate new clinical characteristics and multimodal imaging findings in patients from different ethnic origins, carrying different mutations. METHODS: Multicenter international retrospective case series of 18 patients with genetically confirmed RDH5-related fundus albipunctatus. Patients' files were reviewed for fundus images, visual acuity, macular optical coherence tomography scans, near-infrared images, fundus autofluorescence, electroretinogram, and genetic mutations. Imaging and electroretinogram findings. RESULTS: All eyes (n = 36, 100%) showed small circular findings seen on near-infrared images, termed as the "target sign," correlating to the yellowish dots seen clinically and to the distinct hyperreflective linear lesions on optical coherence tomography at the level between external limiting membrane and retinal pigment epithelium. Perifoveal atrophy with foveal sparing was seen in 4 eyes of 2 patients (both RDH5-c.160C>T, p.R54X mutation). Fundus autofluorescence revealed small hyperautofluorescent dots (n = 16, 44.4%). Scotopic electroretinograms were significantly reduced in all cases with an electronegative pattern, 66.7% displayed cone dysfunction. CONCLUSION: Our results show distinct imaging findings present in all patients with fundus albipunctatus independent of ethnicity or genetic mutation. Our results can facilitate the current algorithm to diagnose RDH5-related fundus albipunctatus and allow for targeted genetic testing.

Thicker macula in asymptomatic APOE Ɛ4 middle-aged adults at high AD risk.

INTRODUCTION: We compared retinal layers' thickness between apolipoprotein E (APOE) Ɛ4 carriers and non-carriers in a cohort of cognitively normal middle-aged adults enriched for Alzheimer's disease (AD) risk. METHODS: Participants (N = 245) underwent spectral domain optical coherence tomography. Multivariate analyses of covariance adjusting for age, sex, education, and best corrected vision acuity was used to compare retinal thickness between APOE groups. RESULTS: Participants' mean age was 59.60 (standard deviation = 6.42) with 66.4% women and 32.2% APOE Ɛ4 carriers. Greater macular full thickness was observed in APOE Ɛ4 carriers compared to non-carriers (P = .017), reaching statistical significance for the inner and outer nasal (P = .009 and P = .005, respectively), inner superior (P = .041), and inner and outer inferior (P = .013 and P = .033, respectively) sectors. The differences between APOE groups were mainly driven by the ganglion cell layer (P < .05) and the inner plexiform layer (P < .05). DISCUSSION: A thicker macula is observed already in midlife asymptomatic APOE Ɛ4 carriers at high AD risk.

Intrinsic Expression of Coagulation Factors and Protease Activated Receptor 1 (PAR1) in Photoreceptors and Inner Retinal Layers.

The aim of this study was to characterize the distribution of the thrombin receptor, protease activated receptor 1 (PAR1), in the neuroretina. Neuroretina samples of wild-type C57BL/6J and PAR1-/- mice were processed for indirect immunofluorescence and Western blot analysis. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to determine mRNA expression of coagulation Factor X (FX), prothrombin (PT), and PAR1 in the isolated neuroretina. Thrombin activity following KCl depolarization was assessed in mouse neuroretinas ex vivo. PAR1 staining was observed in the retinal ganglion cells, inner nuclear layer cells, and photoreceptors in mouse retinal cross sections by indirect immunofluorescence. PAR1 co-localized with rhodopsin in rod outer segments but was not expressed in cone outer segments. Western blot analysis confirmed PAR1 expression in the neuroretina. Factor X, prothrombin, and PAR1 mRNA expression was detected in isolated neuroretinas. Thrombin activity was elevated by nearly four-fold in mouse neuroretinas following KCl depolarization (0.012 vs. 0.044 mu/mL, p = 0.0497). The intrinsic expression of coagulation factors in the isolated neuroretina together with a functional increase in thrombin activity following KCl depolarization may suggest a role for the PAR1/thrombin pathway in retinal function.

Suprachoroidal delivery of bevacizumab in rabbit in vivo eyes: Rapid distribution throughout the posterior segment.

PURPOSE: To test the in-vivo bio-distribution and safety of bevacizumab delivery into the suprachoroidal space (SCS) using a novel injection system in a large eye model. METHODS: Bevacizumab (1.25 mg) was injected into the vitreous (IVT, 50 µL, n = 12) or the SCS, (150 µL, n = 37) of live rabbits. Immunofluorescence and ELISA were used to assess bevacizumab distribution. Intraocular pressure (IOP) measurements, SD-OCT and fundus imaging, electroretinogram, and histology analysis were performed for safety assessment. RESULTS: Bevacizumab was observed throughout the choroid layers up to the retinal pigment epithelium (RPE), within 1 h following SCS injection. The Cmax of bevacizumab in the retina/choroid was 1043 ± 597 µg/gr tissue (mean ± standard error), 40-fold higher than in IVT injected eyes (p = 0.0339). One day following SCS injection, bevacizumab was detected throughout the posterior pole with a two-fold lower concentration. One week post-SCS injection, bevacizumab concentration in the retina/choroid dropped to 2.36 ± 1.32 µg/gr tissue (p = 0.034 vs. 1 h), with a half-life of 20 h. No suprachoroidal blebs, retinal detachment, hemorrhages, inflammation or changes in retinal function were observed up to 2 months following SCS injection. Elevated IOP (+16 mmHg) was observed two minutes post-SCS injection and spontaneously returned to baseline levels within 10 minutes. CONCLUSIONS: The novel injection system enabled a minimally invasive, safe, and consistent delivery of bevacizumab with rapid distribution throughout the choroid layers up to the RPE in large eyes. Large volumes of anti-angiogenic are delivered in close proximity to the retina due to the high volume distribution.

Ophthalmic emergency-room visits during the Covid-19 pandemic - a comparative study.

BACKGROUND: The goal of this study is to compare ophthalmic emergency room (OER) visits during the Coronavirus disease-19 (Covid-19) pandemic to those during a control period. METHODS: We compared all visits to the OER to Meir Medical Center in Israel, from March 15th to April 15th, 2020, during the Covid-19 pandemic and government mandated quarantine, to the same period in 2019. Factors analyzed were patient demographics, chief complaints, referral patterns, exam findings, treatments given, hospitalizations and surgical interventions. RESULTS: We included in this study 1311 visits of 1158 patients, 477 during the 2020 Covid-19 pandemic and 834 during the same period in 2019. The demographic distribution (age, gender, and ethnicity) was similar between the two periods. LogMAR visual acuity at presentation was worse during the Covid-19 pandemic (0.42 ± 0.6 and 0.34 ± 0.5 in 2020 and 2019 respectively; p = 0.025) and the number of emergent surgeries was higher (3.7% in 2020 vs 1.8% in 2019, p = 0.026). In 2019 there was a higher likelihood of involvement of both segments of the eye (4.82% versus 1.2%, p < 0.01) and more diagnoses were given to each patient (1 ± 0.5 versus 0.93 ± 0.35, p = 0.001; During the Covid - 19 pandemic medications (both topical and systemic) were prescribed more often (1.22 ± 0.95 in 2020 and 0.84 ± 0.67 in 2019, p < 0.001). CONCLUSIONS: OER visits were less frequent during the Covid - 19 pandemic as compared to 2019, though the demographics of the patients remained unchanged. Visits during the pandemic tended to be for more severe ocular conditions, with worse visual acuity at presentation and required more medical and surgical treatment which imply higher necessity of ocular evaluation. This analysis can aid healthcare resource management in similar scenarios in the future.

Surgical outcomes of Ahmed glaucoma valve implantation with plate fixation using vicryl sutures or no plate fixation.

PURPOSE: To summarize the surgical outcomes of Ahmed glaucoma valve (AGV) implantation with plate fixation with vicryl absorbable sutures or no plate suturing. METHODS: This study was a retrospective case series that included all glaucoma patients who underwent AGV implantation surgery with vicryl absorbable sutures for plate fixation or without plate fixation by a single surgeon between 2014 and 2019. We reviewed their medical records and retrieved clinical data on intra- and postoperative complications, best-corrected visual acuity, intraocular pressure (IOP), and number of IOP-lowering medications. RESULTS: Twenty out of 29 eyes (29 patients, mean age 61.04 ± 27.1 years, 17 men) underwent AGV implantation without plate fixation and nine had AGV implantation with fixation with vicryl sutures. Complications were observed in 15 cases (51.7%). Nine of these were defined as failure due to the need for removal or repositioning of the AGV or for further surgery for uncontrolled IOP, of which five were no-fixation cases (5/20, 25%) and four were vicryl-fixation cases (4/9, 44.4%). Six of all surgical failures were related to AGV migration (6/9, 66.6%). There were three cases of extrusion and one case of plate migration in the no-fixation group, and two cases of plate migration and one case of extrusion in the vicryl-fixation group. CONCLUSION: AGV implantation without suture plate fixation or with vicryl suture fixation had a high complication and failure rate, often necessitating reoperation and AGV removal. The high rate of tube-related complications observed after both techniques does not favor either of them. The use of non-absorbable sutures for suturing of the AGV plate is recommended.

In vivo retinal imaging in translational regenerative research.

Regenerative translational studies must include a longitudinal assessment of the changes in retinal structure and function that occur as part of the natural history of the disease and those that result from the studied intervention. Traditionally, retinal structural changes have been evaluated by histological analysis which necessitates sacrificing the animals. In this review, we describe key imaging approaches such as fundus imaging, optical coherence tomography (OCT), OCT-angiography, adaptive optics (AO), and confocal scanning laser ophthalmoscopy (cSLO) that enable noninvasive, non-contact, and fast in vivo imaging of the posterior segment. These imaging technologies substantially reduce the number of animals needed and enable progression analysis and longitudinal follow-up in individual animals for accurate assessment of disease natural history, effects of interventions and acute changes. We also describe the benefits and limitations of each technology, as well as outline possible future directions that can be taken in translational retinal imaging studies.

Chromatic Pupilloperimetry Measures Correlate With Visual Acuity and Visual Field Defects in Retinitis Pigmentosa Patients.

Purpose: To evaluate the ability of chromatic pupilloperimetry to identify visual field (VF) defects in patients with retinitis pigmentosa (RP) and to test the correlation between pupilloperimetry impairment and retinal structural and functional measures. Methods: The pupil responses of 10 patients with RP (mean age, 41.3 ± 16.2 years) and 32 healthy age-similar controls (mean age, 50.7 ± 15.5 years) for 54 focal blue and red stimuli presented in a 24-2 VF were recorded. The pupilloperimetry measures were correlated with Humphrey VF mean deviation, best-corrected visual acuity, and ellipsoid zone area. Results: Substantially lower percentage of pupil contraction and maximal pupil contraction velocity (MCV) were recorded in patients with RP throughout the VF in response to blue and red stimuli. The mean absolute deviation (MADEV) in the latency of MCV (LMCV) was significantly larger in patients compared with controls for blue and red stimuli (P = 1.0 × 10-7 and P = 1.0 × 10-6, respectively). The LMCV MADEV differentiated between patients and controls with high specificity and sensitivity (area under the receiver operating characteristic curve, 0.987 and 0.973 for blue and red, respectively). The MADEV of LMCV for blue stimuli correlated with best-corrected visual acuity (ρ = 0.938, P = 5.9 × 10-5) and ellipsoid zone area (ρ = -0.857; P = 0.002). The MADEV of LMCV for red stimuli correlated with Humphrey VF mean deviation (ρ = -0.709; P = 0.022). Minimizing the test to 15 targets maintained a diagnosis of retinal damage in patients with RP with high sensitivity and specificity (area under the receiver operating characteristic curve, 0.927). Conclusions: The chromatic pupilloperimetry measures significantly correlated with retinal function and structure in patients with RP at various disease stages. Translational Relevance: Chromatic pupilloperimetry may enable objective assessment of visual field defects and visual acuity in RP.

Efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid using a blunt adjustable depth injector.

PURPOSE: To evaluate the efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid (EVSC) in rabbit eyes in vivo using a blunt adjustable depth injector. METHODS: Indocyanine green (ICG) was injected in the superior-temporal quadrant, 2 mm posterior to the limbus at increasing volumes (0.1-0.3 ml) into the EVSC of New Zealand rabbit eyes in vivo. Intraocular pressure (IOP) measurements, spectral domain optical coherence tomography (SD-OCT), fundus imaging and histology analysis were performed to assess the safety and efficacy of the injection. RESULTS: Volumes up to 0.3 ml were administered consistently. ICG injection was successfully monitored in vivo using infrared fundus imaging and SD-OCT. ICG was detected across the EVSC compartment, reaching the retinal pigment epithelium, optic nerve head and visual streak. Injection of 0.3 ml yielded maximal dye distribution with a coverage area of 61.8% ± 6.7% (mean ± standard error, SE) of the posterior segment. Maximal IOP elevation was recorded 5 min following injection of 0.2 and 0.3 ml ICG (+ 20.0 mmHg, + 19.4 mmHg, respectively). Twenty minutes post-injection, the IOP was < 15 mmHg in all injection volumes. No retinal detachment or hemorrhages were detected in any of the injected eyes. CONCLUSIONS: This study demonstrates consistent and safe delivery of large volumes within the EVSC using a blunt adjustable depth injector that distributes the dye over 60% of the retinal surface. This injection system may offer a minimally invasive and easy way to deliver large volumes of pharmaceuticals into the posterior segment.

Topical Estrogen Therapy for Hyperopia Correction in Vivo.

Purpose: In vitro studies found that 17ß-estradiol (estrogen) modulates corneal biomechanical properties and reduces tissue stiffness. Therefore we hypothesized that topical estrogen might affect the refractive properties of the cornea, inducing a myopic shift. Methods: Twelve female New Zealand white rabbits 16 weeks old were used. The rabbits were randomly divided to either the treatment group receiving 1.5% (w/v) estrogen eye drops or a control group receiving vehicle only (n = 6 each group). Both groups were given drops (50 µL) to the right eye every 12 hours for 35 days. Ocular examination, pachymetry, intraocular pressure (IOP), keratometry ,and refraction were evaluated at baseline and on a weekly basis. Results: No significant differences were observed between the two groups at baseline in all outcome measures. Both groups displayed corneal flattening and a hyperopic shift. However, the change rate was slower in the treatment group. Repeated measurements analysis revealed a statistically significant difference in keratometry readings between groups (P = 0.034) with steeper keratometry by up to 0.6 diopters in the treatment group. The difference between the two groups diminished and became statistically insignificant after treatment cessation. No significant changes were observed in IOP and pachymetry throughout the study period. No side effects were observed in either group. Conclusions: Estrogen eye drops induced a myopic shift in keratometry readings. These results suggest that corneal refractive power might be manipulated pharmacologically. Further studies on the physiology behind this change are warranted to facilitate a pathway for development of novel pharmacologic treatments to correct refractive errors.

High-intensity Focused Ultrasound Treatment in Moderate Glaucoma Patients: Results of a 2-Year Prospective Clinical Trial.

PRECIS: Ultrasound Cyclo Plasty (UCP) treatment using high-intensity focused ultrasound (HIFU) is an effective and safe therapy to reduce intraocular pressure (IOP) in moderate glaucoma patients as was measured during a 2-year follow-up period. PURPOSE: The purpose of this study was to evaluate the long-term safety and efficacy of the UCP procedure using HIFU in moderate glaucoma patients. PATIENTS AND METHODS: A prospective interventional noncomparative study was carried out. Fifteen patients (15 eyes) with moderate open-angle glaucoma were enrolled. All eyes were treated with UCP-HIFU. A thorough ophthalmic examination and IOP measurements were performed before the UCP-HIFU procedure and at 1 day, 1 week, 4 weeks, 3 months, 6 months, 1 year, and 2 years after the procedure. The primary outcome was defined as a surgical success (IOP reduction of 20% or ≥5 mm Hg) at the last follow-up visit. The secondary outcomes were the mean IOP at each follow-up visit, number of medications used, complications profile, and reinterventions. RESULTS: The mean preoperative IOP at baseline was 26.8±5.0 mm Hg. All patients had a positive response and a lower IOP after treatment, with a relatively stable 31% reduction in IOP during the follow-up period. A significant reduction in IOP was observed at all postprocedure examination points (P<0.01), with a mean 17.6±4.4 mm Hg at 2 years after the procedure (P=0.005). Surgical success was achieved in 87% of the patients at their last follow-up visit. There was a nonsignificant decrease in the mean number of glaucoma medications from 2.5±0.8 to 2.0±1.0 at 2 years (P=0.48). No major intraoperative or postoperative complications were noted. CONCLUSION: UCP-HIFU treatment is an effective, safe, and well-tolerated method to reduce IOP in patients with moderate glaucoma.