ULTRA-WIDEFIELD IMAGING DETECTION RATE IN IDENTIFYING PERIPHERAL RETINAL TEARS IN SINGLE VERSUS MONTAGE OF PERIPHERAL STEERING.

PURPOSE: To compare the detection rate of orthogonal, directed peripheral steering, and automontaged images with ultra-widefield imaging and the factors influencing the ability to identify retinal breaks. DESIGN: Retrospective cohort study. METHODS: Three hundred and seventy-six treatment-naive eyes (349 patients) that underwent laser retinopexy for retinal breaks between 2015 and 2021 were included. Pretreatment ultra-widefield orthogonal, peripheral steering, and automontage were cross-referenced to scleral-depressed examination to determine whether images successfully visualized all retinal breaks. Total relative retinal area (RRA) visualized was divided by its optic disk area (pixels) to calculate relative retinal area. Potential associations were assessed by linear regression analysis. RESULTS: One hundred and sixty two eyes (154 patients) met inclusion criteria. Orthogonal, peripheral steering, and automontage images showed detection rates of 47.5%, 90.7%, and 80.0%, respectively. Relative retinal area increased from orthogonal versus montage by 34.7% ± 26.5% (mean ± SD), which increased the detection rate by 90.8% ( P = 0.006). In linear probability models, vertical meridian tears decreased probability of identification in orthogonal, peripheral steering, and automontage by -26.6%, -86.2%, and -68.7%, respectively ( P < 0.001), and horizontal meridian tears increased the probability by 62.2%, 92.9%, and 85.5%, respectively, ( P < 0.001). Tears posterior to the equator in orthogonal images increased the probability (91.4%, P < 0.001). Artifacts such as lids/lashes, reflection, and face guard decreased the probability in directed peripheral steering by -28.6%, -50.0%, and -66.7%, respectively, ( P = 0.020, P = 0.049, and P = 0.016). CONCLUSION: Using directed peripheral steering and automontage increases RRA and detection rate of identifying peripheral retinal breaks. Tears in horizontal meridians or posterior to the equator increase the probability of identification. Common ultra-widefield imaging artifacts can significantly limit the probability of identifying retinal tears.

In-vivo high-frequency quantitative ultrasound-derived parameters of the anterior sclera correlated with level of myopia and presence of staphyloma.

BACKGROUND: A high-frequency point-of-care (POC) ultrasound instrument was used to evaluate the microstructural and biomechanical properties of the anterior sclera in vivo using parameters computed from quantitative ultrasound (QUS) methods. METHODS: In this cross-sectional study, both eyes of 85 enrolled patients were scanned with the POC instrument and ultrasound data were processed to obtain QUS parameters. Pearson correlation and multi-linear regression were used to identify relationships between QUS parameters and refractive error (RE) or axial length. After categorising eyes based on RE, binary support vector machine (SVM) classifiers were trained using the QUS or ophthalmic parameters (anterior chamber depth, central corneal thickness, corneal power, and intraocular pressure) to classify each eye. Classifier performance was evaluated by computing the area under the receiver-operating characteristic curve (AUC). RESULTS: Individual QUS parameters correlated with RE and axial length (p < 0.05). Multi-linear regression revealed significant correlation between the set of QUS parameters and both RE (R = 0.49, p < 0.001) and axial length (R = 0.46, p = 0.001). Classifiers trained with QUS parameters achieved higher AUC (𝑝 = 0.06) for identifying myopic eyes (AUC = 0.71) compared to classifiers trained with ophthalmic parameters (AUC = 0.63). QUS-based classifiers attained the highest AUC when identifying highly myopic eyes (AUC = 0.77). CONCLUSIONS: QUS parameters correlate with progressing myopia and may be indicative of myopia-induced microstructural and biomechanical changes in the anterior sclera. These methods may provide critical clinical information complementary to standard ophthalmic measurements for predicting myopia progression and risk assessment for posterior staphyloma formation.

High-frequency ultrasound point-of-care device to quantify myopia-induced microstructural changes in the anterior sclera.

PURPOSE: To develop a point-of-care (POC) device using high-frequency ultrasound (US) for evaluating microstructural changes in the anterior sclera associated with myopia. METHODS: The proposed POC device must satisfy four primary requirements for effective clinical use: the measurement component is handheld; the software must be simple and provide real-time feedback; patient safety and health data security requirements set forth by relevant governing bodies must be satisfied and the measurement data must have sufficient signal-to-noise ratio (SNR) and repeatability. Radiofrequency (RF) echo data acquired by the POC device will be processed using our quantitative US methods to characterise tissue microstructure and biomechanical properties. RESULTS: All stated requirements have been met in the developed POC device. The high-frequency transducer is housed in a custom, 3D-printed, pen-like holder that allows for easy measurements of the anterior sclera. Custom software provides a simple interface for data acquisition, real-time data display and secure data storage. Exposimetry measurements of the US pressure field indicate device compliance with United States Food and Drug Administration limits for ophthalmic US. In vivo measurements on a volunteer suggest the RF data SNR and acquisition consistency are suitable for quantitative analysis. CONCLUSIONS: A fully functioning POC device using high-frequency US has been created for evaluating the microstructure of the anterior sclera. Planned studies using the POC device to scan the eyes of myopia patients will help clarify how the anterior sclera microstructure may be affected by myopia. If effective, this portable, inexpensive and user-friendly system could be an important part of routine eye examinations.

The Potential of Current Polygenic Risk Scores to Predict High Myopia and Myopic Macular Degeneration in Multiethnic Singapore Adults.

PURPOSE: To evaluate the transancestry portability of current myopia polygenic risk scores (PRSs) to predict high myopia (HM) and myopic macular degeneration (MMD) in an Asian population. DESIGN: Population-based study. PARTICIPANTS: A total of 5894 adults (2141 Chinese, 1913 Indian, and 1840 Malay) from the Singapore Epidemiology of Eye Diseases study were included in the analysis. The mean ± standard deviation age was 57.05 ± 9.31 years. A total of 361 adults had a diagnosis of HM (spherical equivalent [SE] < -5.00 diopters [D]) from refraction measurements, 240 individuals had a diagnosis of MMD graded by the International Photographic Classification and Grading System for Myopic Maculopathy criteria from fundus photographs, and 3774 individuals were control participants without myopia (SE > -0.5 D). METHODS: The PRS, derived from 687 289 HapMap3 single nucleotide polymorphisms (SNPs) from the largest genome-wide association study of myopia in Europeans to date (n = 260 974), was assessed on its ability to predict patients with HM and MMD versus control participants. MAIN OUTCOME MEASURES: The primary outcomes were the area under the receiver operating characteristic curve (AUC) to predict HM and MMD. RESULTS: The PRS had an AUC of 0.73 (95% confidence interval [CI], 0.70-0.75) for HM and 0.66 (95% CI, 0.63-0.70) for MMD versus no myopia. The inclusion of the PRS with other predictors (age, sex, educational attainment [EA], and ancestry; age-by-ancestry, sex-by-ancestry, and EA-by-ancestry interactions; and 20 genotypic principal components) increased the AUC to 0.84 (95% CI, 0.82-0.86) for HM and 0.79 (95% CI, 0.76-0.82) for MMD. Individuals with a PRS in the top 5% showed up to a 4.66 (95% CI, 3.34-6.42) times higher risk of HM developing and up to a 3.43 (95% CI, 2.27-5.05) times higher risk of MMD developing compared with the remaining 95% of individuals. CONCLUSIONS: The PRS is a good predictor for HM and facilitates the identification of high-risk children to prevent myopia progression to HM. In addition, the PRS also predicts MMD and helps to identify high-risk adults with myopia who require closer monitoring for myopia-related complications.

Biomechanical changes in myopic sclera correlate with underlying changes in microstructure.

Myopia alters the microstructural and biomechanical properties of the posterior sclera, which is characterized as a layered structure with potentially different inter-layer collagen fibril characteristics. Scanning acoustic microscopy (SAM) has been used to investigate how the micron-scale bulk mechanical properties of the posterior sclera are affected by myopia. Other investigators have employed second harmonic generation (SHG) imaging to characterize the collagen microstructure of tissues. In the present study, SAM and SHG imaging were used to investigate the existence of biomechanically-distinct scleral layers and identify relationships between mechanical properties and tissue microstructure in myopic guinea pig (GP) eyes. Diffusers were worn over the right eyes of six, 1-week-old GPs for one week to induce unilateral form-deprivation myopia. GPs were euthanized, enucleated, and eyes were cryosectioned. Twelve-micron-thick adjacent vertical cryosections were scanned with SAM or SHG. SAM maps of bulk modulus, mass density, and acoustic attenuation were estimated. A fiber-extraction algorithm applied to SHG images estimated collagen fiber length, width, straightness, alignment, and number density. Results revealed that the posterior sclera may exhibit biomechanically distinct layers that are affected differently in myopia. Specifically, a layered structure was observed in the mechanical-parameter maps of control eyes that was less apparent in myopic eyes. Collagen fibers in myopic eyes had smaller diameters and were more aligned. Myopia-associated biomechanical changes were most significant in the outermost and innermost scleral layers. SAM-measured mechanical parameters were correlated with collagen fiber microstructure, particularly fiber length, alignment, and number density, which may imply the biomechanical parameters estimated from SAM measurements are related to tissue microstructure. Interestingly, some changes were greatest in more-peripheral regions, suggesting interventions to strengthen the sclera may be effective away from the optic nerve and efficacy may be achieved best when intervention is applied to the outermost layer.

MACULAR SENSITIVITY AND CAPILLARY PERFUSION IN HIGHLY MYOPIC EYES WITH MYOPIC MACULAR DEGENERATION.

PURPOSE: To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD). METHODS: One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length. RESULTS: Macular sensitivity reduced with increasing severity of MMD (ß ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (ß = -0.08, P < 0.001), with longer axial length (ß = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (ß = -2.16, P < 0.001) or worse MMD (ß = -5.70, P < 0.001), and presence of macular posterior staphyloma (ß ≤ -2.98, P < 0.001) or Fuchs spot (ß = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (ß = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62). CONCLUSION: There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.

BACILLARY LAYER DETACHMENT BECAUSE OF MACULAR NEOVASCULARIZATION.

PURPOSE: To describe the clinical and multimodal imaging features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor therapy, in eyes with macular neovascularization. METHODS: Retrospective, observational case series of 14 eyes (14 patients, 7 men) imaged with eyes (14 patients, 7 men) were imaged with spectral-domain optical coherence tomography, and either fluorescein angiography or optical coherence tomography angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity assessments. RESULTS: The mean age was 75 ± 13 (range: 45-96) years, with mean follow-up duration of 27 ± 21 (range: 1-56) months. Neovascular age-related macular degeneration was found in 71% (10/14) eyes. Type 2 macular neovascularization lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved after intravitreal antivascular endothelial growth factor therapy in all eyes. The baseline best-corrected visual acuity improved from logarithm of the minimum angle of resolution 0.84 ± 0.32 (Snellen equivalent 20/138) to logarithm of the minimum angle of resolution 0.48 ± 0.31 (Snellen equivalent 20/60) at the last follow-up, with treatment of the macular neovascularization. CONCLUSION: Type 2 macular neovascularization and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal antivascular endothelial growth factor therapy results in rapid resolution of BDs and visual improvement in most eyes.

CORRELATION OF EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AVERAGING VERSUS SINGLE-IMAGE QUANTITATIVE MEASUREMENTS WITH RETINAL VEIN OCCLUSION VISUAL OUTCOMES.

PURPOSE: To demonstrate the effect of averaging multiple en face optical coherence tomography angiography images on the correlation between retinal microvasculature quantitative metrics and best-corrected visual acuity (BCVA) in eyes with retinal vein occlusion. METHODS: A cross-sectional cohort with unilateral retinal vein occlusion was imaged in both eyes. Five 3 mm × 3-mm spectral domain optical coherence tomography angiography images were averaged, and quantitative parameters from averaged versus single images were correlated with logMAR BCVA. Regression analyses were performed to correlate quantitative metrics with BCVA. RESULTS: Ten patients (5 male, average age 64.3 years) were included. Among retinal vein occlusion eyes, vessel length density was significantly less in averaged versus a single image for both the superficial retinal layer (15.5 ± 2.5 vs. 17.8 ± 2.4/mm, P = 0.05) and deep retinal layer (16.2 ± 1.4 vs. 18.5 ± 1.6/mm, P = 0.003). Multivariate linear regression showed an increased R value with averaging (0.93 to 0.95, for single and averaged groups, respectively). Foveal avascular zone circularity was associated with BCVA on single images (coefficient = -0.96, P = 0.002), but not with averaged images (P = 0.063). CONCLUSION: Scan averaging of en face optical coherence tomography angiography images improves the clarity of vessels and may allow for more accurate quantification of vessel metrics. Quantitative metrics are significantly associated with BCVA, and averaging does not further improve this association compared with single-scan analysis.

Regional changes in the elastic properties of myopic Guinea pig sclera.

Biomechanical changes in the sclera likely underlie the excessive eye elongation of axial myopia. We studied the biomechanical characteristics of myopic sclera at the microscopic level using scanning acoustic microscopy (SAM) with 7-µm in-plane resolution. Guinea pigs underwent form-deprivation (FD) in one eye from 4 to 12 days of age to induce myopia, and 12-µm-thick scleral cryosections were scanned using a custom-made SAM. Two-dimensional maps of the bulk modulus (K) and mass density (ρ) were derived from the SAM data using a frequency-domain approach. We assessed the effect on K and ρ exerted by: 1) level of induced myopia, 2) region (superior, inferior, nasal or temporal) and 3) eccentricity from the nerve using univariate and multivariate regression analyses. Induced myopia ranged between -3D and -9.3D (Mean intraocular difference of -6.2 ±â€¯1.7D, N = 11). K decreased by 0.036 GPa for every 1.0 D increase in induced myopia across vertical sections (p < 0.001). Among induced myopia right eyes, K values in the inherently more myopic superior region were 0.088 GPa less than the inferior region (p = 0.002) and K in the proximal nasal region containing the central axis were 0.10 GPa less than temporal K (p = 0.036). K also increased 0.12 GPa for every 1 mm increase in superior vertical distance (p < 0.001), an effect that was blunted after 1 week of FD. Overall, trends for ρ were less apparent than for K. ρ values increased by 20.7 mg/cm3 for every 1.00 D increase in induced myopia across horizontal sections (p < 0.001), and were greatest in the region containing the central posterior pole. ρ values in the inherently more myopic superior region were 13.1 mg/cm3 greater than that found in inferior regions among control eyes (p = 0.002), and increased by 11.2 mg/cm3 for every 1 mm increase in vertical distance (p = 0.001). This peripheral increase in ρ was blunted after 1 week of FD. Scleral material properties vary depending on the location in the sclera and the level of induced myopia. Bulk modulus was most reduced in the most myopic regions (both induced myopia and inherent regional myopia), and suggests that FD causes microscopic local decreases in sclera stiffness, while scleral mass density was most increased in the most myopic regions.

PROPHYLACTIC PREOPERATIVE LASER RETINOPEXY DOES NOT REDUCE THE OCCURRENCE OF RHEGMATOGENOUS RETINAL COMPLICATIONS IN MACULAR SURGERY.

PURPOSE: Knowledge on the utility of prophylactic 360° laser retinopexy before pars plana vitrectomy in the absence of peripheral retinal pathology is limited. This study compares the occurrence of rhegmatogenous events in the setting of small-gauge pars plana vitrectomy with and without prophylactic preoperative laser. METHODS: Our multicenter, retrospective case-control analysis reviewed patients who underwent epiretinal membrane removal or macular hole repair through 23- or 25-gauge pars plana vitrectomy: 205 controls who did not receive prophylactic laser and 176 cases who received preoperative prophylactic laser retinopexy anterior to the equator. Main outcome measures were the rate and characteristics of postoperative retinal tears and detachments. Patients with previous pars plana vitrectomy or significant retinal disease were excluded. RESULTS: Of those patients with prophylactic laser and those without, there was no significant difference in the number of retinal breaks (1.7% vs. 0.49%, respectively; P = 0.339) or retinal detachments (0% vs. 0.49%, respectively; P = 1.00). Of the lasered group, there was one sclerotomy-related retinal break and two non-sclerotomy-related retinal breaks. Of the nonlasered group, there was one non-sclerotomy-related retinal break and one sclerotomy-related retinal detachment. CONCLUSION: Preoperative prophylactic peripheral laser retinopexy does not seem to offer an added benefit in the prevention of intraoperative and postoperative rhegmatogenous events.

Longitudinal Changes in Disc and Retinal Lesions Among Highly Myopic Adolescents in Singapore Over a 10-Year Period.

OBJECTIVES: To examine the progression pattern of disc and retinal lesions in highly myopic Chinese adolescents over a 10-year period in Singapore. METHODS: This longitudinal study included Chinese participants who showed high myopia (spherical equivalent [SE] worse than or equal to -5 diopters [D]), no history of refractive surgery, and available fundus photographs at both 2006 (baseline) and 2016 (10-year follow-up) visits. Forty-four adolescents (aged 12-16 years at baseline) who were re-examined later at follow-up were included. Cycloplegic refraction, biometry, and fundus photography were performed at both visits. A trained grader classified myopic macular degeneration (MMD) based on the Meta-pathologic myopia classification and disc lesions from fundus photographs. Choroidal thickness (CT) measurements were performed at 10-year follow-up using swept-source optical coherence tomography. The ocular parameters and lesions were compared between baseline and follow-up. RESULTS: There was a significant worsening of high myopia at follow-up to -7.5±1.8 D (mean SE±SD) in 2016 versus -6.2±1.3 D in 2006; (P<0.001). The 10-year changes included increased degree of tessellation (26 eyes, 29.5%), development of new tessellated fundus (19 eyes, 21.6%), disc tilt (7 eyes, 8.0%), and expansion of peripapillary atrophy size (33 eyes, 37.5%). Eyes with early-onset tessellation (present at baseline, 48 eyes) showed significantly thinner CT (P<0.05), compared with eyes with late-onset tessellation (incident at 10-year follow-up, 19 eyes). No cases of MMD were recorded at baseline or 10-year follow-up. CONCLUSIONS: Although there was no incident MMD, the retinal and disc lesions worsened over the follow-up period. Early-onset fundus tessellation was associated with thinner CT.

ASSESSMENT OF THE SIGNIFICANCE OF CYSTIC CHANGES AFTER EPIRETINAL MEMBRANE SURGERY WITH INTERNAL LIMITING MEMBRANE REMOVAL.

PURPOSE: To assess the prevalence and significance of cystic changes after internal limiting membrane peeling during epiretinal membrane surgery. METHODS: A retrospective review was performed on 64 patients who underwent pars plana vitrectomy with membranectomy for idiopathic epiretinal membrane between January 2010 and January 2012 by a single physician. Pars plana vitrectomy alone (Group 1, n = 32) or in combination with phacoemulsification (Group 2, n = 32) was performed. Peeling of the epiretinal membrane was assisted by triamcinolone, and internal limiting membrane was peeled up to the vascular arcades with the aid of brilliant blue dye. RESULTS: In Group 1, best-corrected visual acuity in logMAR (Snellen) improved from 0.53 ± 0.29 (20/68) at baseline to 0.23 ± 0.22 (20/34) at 6-month follow-up (P < 0.001). Two cases (6.3%) developed new cystic changes within the inner nuclear layer; however, there was no significant difference in best-corrected visual acuity at 6 months (P = 0.475). In Group 2, best-corrected visual acuity improved from 0.41 ± 0.17 (20/51) at baseline to 0.18 ± 0.15 (20/30) at 6 months (P < 0.001). Eight cases (25%) developed new inner nuclear layer cystic changes; however, there was no significant difference in best-corrected visual acuity at 6 months (P = 0.894). CONCLUSION: Development of new inner nuclear layer cystic changes after epiretinal membrane surgery may be a frequent finding, but in contrast to cystoid macular edema, it does not seem to affect visual recovery and should be observed. The combination of pars plana vitrectomy with cataract extraction may increase the risk of inner nuclear layer cystic changes.

LONG-TERM RETROSPECTIVE ANALYSIS OF VISUAL ACUITY AND OPTICAL COHERENCE TOPOGRAPHIC CHANGES AFTER SINGLE VERSUS DOUBLE PEELING DURING VITRECTOMY FOR MACULAR EPIRETINAL MEMBRANES.

PURPOSE: To determine the long-term effect of internal limiting membrane with associated epiretinal membrane (ERM) peeling versus single peeling alone in terms of best-corrected visual acuity and anatomical outcomes on spectral-domain optical coherence tomography. METHODS: This retrospective comparative cohort study of patients who had follow-up of >1 year and underwent surgery for ERM by a single surgeon (S.C.) from January 1, 2008 to December 31, 2012 compared cases in which the internal limiting membrane was stained with brilliant blue G to facilitate double peeling (n = 42) and single peeling (n = 43) of the ERM alone for up to 3 years of follow-up. For continuous variables, an independent two-tailed t-test was performed. For binary variables, the Fisher's exact test was performed. Statistical significance was defined as P < 0.05. RESULTS: Eighty-five of 142 patients fit the inclusion criteria. At the last follow-up, the single-peeling group were more likely to have ERM remaining in the central fovea postoperatively (P = 0.0020, becoming significant by postoperative Year 1, P = 0.022) and less likely to develop inner retinal dimpling (P = 0.000, becoming significant by postoperative Month 3, P = 0.015). At 3 years, central foveal thickness had decreased in the single-peeling group by -136.9 µm and by -84.1 µm in the double-peeling group, which was not significantly different (P = 0.08). Mean best-corrected visual acuity improved in both the groups at all time points. There was no statistically significant difference between the 2 groups at 3 years (P = 0.44; single-peeling group, 0.32 ± 0.42, Snellen 20/42; double-peeling group, 0.23 ± 0.27, Snellen 20/34). CONCLUSION: Brilliant blue G-assisted internal limiting membrane peeling for ERM results in a more thorough removal of residual ERM around the paracentral fovea. However, there is no difference in long-term best-corrected visual acuity at 3 years and a greater likelihood of inner retinal dimpling.

Intraocular Pressure in Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept or Ranibizumab.

PURPOSE: To assess change in intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (NVAMD) receiving intravitreal aflibercept injection (IAI) or ranibizumab in VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2 studies. DESIGN: Analyses from 2 randomized, active-controlled, phase III trials. PARTICIPANTS: A total of 2457 patients with NVAMD. METHODS: Patients received IAI 2 mg every (q) 4 weeks (2q4), 0.5 mg q4 weeks (0.5q4), 2 mg q8 weeks (after 3 monthly doses; 2q8), or ranibizumab 0.5 mg q4 weeks (Rq4) for 52 weeks. At week 52, patients were switched to a variable regimen requiring at least quarterly dosing and allowing interim injections based on anatomic and visual assessment. MAIN OUTCOME MEASURES: Pre-injection IOP was analyzed in study and uninjected fellow eyes from baseline to week 96. Prespecified end points included mean change in IOP from baseline and prevalence of a >21 mmHg and >10 mmHg increase in IOP from baseline. Cumulative incidence of sustained (at 2 consecutive visits) IOP >21 mmHg, a single event of IOP >25 mmHg, and sustained IOP increase from baseline (≥5 mmHg) was also evaluated. RESULTS: Mean IOP change from baseline over 96 weeks in all IAI groups was consistently lower than in the Rq4 group, and this finding was replicated in both trials. In an analysis integrating both studies, the proportion of study eyes with IOP >21 mmHg at week 96 was 20.2%, 14.2%, 12.1%, and 12.5% in Rq4, 2q4, 2q8, and 0.5q4, respectively. Reduction in risk, relative to Rq4, of having sustained IOP >21 mmHg over 96 weeks was 62% (95% confidence interval [CI], 36%-78%), 50% (95% CI, 19%-70%), and 69% (95% CI, 45%-84%) for 2q4, 2q8, and 0.5q4, respectively. Risk reduction in the IAI groups for a sustained IOP increase ≥5 mmHg was 31% (95% CI, 8%-48%), 38% (95% CI, 17%-54%), and 47% (95% CI, 27%-61%), respectively. In uninjected fellow eyes, only sustained IOP >21 mmHg events were higher in the Rq4 group compared with all IAI groups. CONCLUSIONS: Incidence of elevated IOP in eyes with NVAMD was lower in all IAI groups than in the ranibizumab group.

Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein defects.

Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)-specific membrane receptor of unknown function. In patient-specific induced pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its dicistronic partner CTRP5, are critical to the regulation of actin organization. Overexpression of CTRP5 in naïve human RPE cells phenocopied behavior of MFRP-deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP rescued the actin disorganization phenotype and restored apical microvilli in patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE recovered pigmentation and transepithelial resistance. The efficacy of AAV-mediated gene therapy was also evaluated in Mfrp(rd6)/Mfrp(rd6) mice--an established preclinical model of RP--and long-term improvement in visual function was observed in AAV-Mfrp-treated mice. This report is the first to indicate the successful use of human iPS-RPE cells as a recipient for gene therapy. The observed favorable response to gene therapy in both patient-specific cell lines, and the Mfrp(rd6)/Mfrp(rd6) preclinical model suggests that this form of degeneration caused by MFRP mutations is a potential target for interventional trials.

ASSOCIATION BETWEEN NEEDLE SIZE, POSTINJECTION REFLUX, AND INTRAOCULAR PRESSURE SPIKES AFTER INTRAVITREAL INJECTIONS.

PURPOSE: To compare the effect of 30-gauge versus 32-gauge needle size on postinjection reflux and immediate postinjection intraocular pressure (IOP(immed_post)) spikes in eyes injected with anti-vascular endothelial growth factor agents. METHODS: This was a prospective interventional case series of 65 eyes of 54 consecutive patients in a clinical practice setting who received intravitreal anti-vascular endothelial growth factor therapy. All eyes had preinjection IOP, IOP(immed_post), postinjection reflux, and axial lengths recorded. RESULTS: There was a higher incidence of postinjection reflux in eyes injected with 30-gauge (53%) compared with those injected with 32-gauge (13%, P = 0.0007). Among 34 eyes injected with 30-gauge, 16 eyes without appreciable postinjection reflux had mean IOP(immed_post) of 44.3 ± 7.48 mmHg and mean IOP(immed_post) elevation of 29.6 ± 2.10 mmHg, which was significantly higher than the 18 eyes with reflux (mean IOP(immed_post) of 18.8 ± 7.15 mmHg and mean IOP(immed_post) elevation of 4.5 ± 1.74 mmHg, P < 0.0001). Among 31 eyes injected with 32-gauge, 27 eyes without appreciable postinjection reflux had mean IOP(immed_post) of 44.4 ± 10.82 mmHg and mean IOP(immed_post) elevation of 29.5 ± 1.99 mmHg, which was significantly higher than the 4 eyes with reflux (mean IOP(immed_post) of 21.3 ± 8.54 mmHg and mean IOP(immed_post) elevation of 9.5 ± 4.05 mmHg, P < 0.001). The differences in reflux and IOP between the two groups were unrelated to axial lengths (P = 0.451). CONCLUSION: Eyes receiving injections with 32-gauge needles had a lower incidence of postinjection reflux and higher mean IOP immediately after injection.

Influence of axial length and postinjection reflux on sustained intraocular pressure elevation as a result of intravitreal anti-vascular endothelial growth factor therapy.

PURPOSE: To assess an association of axial length (AL) or postinjection reflux with transient or sustained intraocular pressure (IOP) elevation in patients with neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor injections. METHODS: One hundred and forty-seven eyes from 74 consecutive patients with neovascular age-related macular degeneration who presented to a single physician over a 2-month period had ALs measured by IOLMaster. Twenty-one patients had preinjection and immediate postinjection IOP measured and immediate reflux assessed. RESULTS: Overall, 9.5% of eyes had been identified with sustained IOP elevation in our previous study. Axial length did not significantly differ between eyes that had (AL, 23.96 ± 0.66 mm; n = 14) and had not experienced sustained IOP elevation (AL, 23.44 ± 1.24 mm; n = 133; P = 0.12, t-test). By linear regression analysis, the relationship between experiencing sustained IOP elevation and AL was not statistically significant (R² = 0.0165; P = 0.121). The relationship between AL and immediate postinjection IOP elevation was also not statistically significant (R² = 0.0001; P = 0.97). Immediate postinjection IOP increase did differ between eyes without reflux (30.2 ± 9.3 mmHg; n = 12) and those with reflux (1.1 ± 7.2; n = 9; P < 0.001). CONCLUSION: Axial length does not seem to be a predictor of transient or sustained IOP elevation. Repeated trabecular meshwork trauma related to the absence or presence of reflux and immediate postinjection IOP elevation may be a contributing factor.

Late recurrence of myopic foveoschisis after successful repair with primary vitrectomy and incomplete membrane peeling.

PURPOSE: To report three cases of late recurrence of myopic foveoschisis (MF) after initial successful repair with pars plana vitrectomy and membrane peeling to assess the importance of internal limiting membrane peeling. METHODS: A retrospective noncomparative case series was performed of patients who underwent a primary pars plana vitrectomy by a single surgeon with successful resolution of MF, but eventually underwent repeat pars plana vitrectomy for recurrent MF. Best-corrected visual acuity, fundus photography, and optical coherence tomography were obtained at each examination. RESULTS: Three eyes of three patients underwent pars plana vitrectomy for recurrent MF. Myopic foveoschisis recurrence occurred 6, 3.5, and 12 years after the primary vitrectomy, respectively. Repeat vitrectomy with staining and additional peeling of the internal limiting membrane resulted in good anatomical outcome and stabilization of visual acuity in all cases. CONCLUSION: Late recurrence of MF after successful primary vitrectomy is described. Fibrocellular proliferation on residual cortical vitreous or incomplete internal limiting membrane peeling during the initial vitrectomy may underlie recurrence.