Cincinnati Eye Institute

We report a complication of dexamethasone intraocular suspension 9% placed into the capsular bag at the conclusion of cataract surgery. This retrospective case series was performed at an academically affiliated multi-specialty private practice group. Documentation from postoperative visits was evaluated for the development of complications including postoperative pressure spikes, corneal edema, spherule prolapse into the anterior chamber, and changes in pupillary shape. 65 eyes of 45 patients were included in the study. Six of 65 eyes (9.2%) developed pupillary abnormalities, and five of them (83.3%) were preceded by observed prolapse of the dexamethasone spherule into the anterior chamber. In total, nine of 65 eyes (13.8%) demonstrated spherule prolapse, four of which (44.4%) had no effect on pupillary shape. Prolapse of this steroid spherule may correlate with the development of pupillary ovalization, and attempts to eliminate postoperative topical steroids will require delivery systems that prevent steroid-induced iris damage.

In patients with iris deficiencies, surgical placement of a custom, artificial iris improves cosmesis and photic symptoms. When patients have existing intraocular lenses (IOLs) within the capsular bag, iris devices also placed within the capsular bag might change the IOL's effectivity; previous reports suggest a hyperopic shift, but data is limited. This retrospective chart review studied 13 eyes receiving a custom, flexible iris prosthesis fixated into an existing intact capsular bag, separate from prior phacoemulsification. Biometry, IOL data, and pre- and post-operative refraction were collected. For iris prosthesis placement without concomitant procedures, the average change in spherical equivalent was +0.49D; For an aphakic eye receiving a secondary IOL, post-operative refraction was +0.79D more hyperopic than expected. For eyes undergoing concomitant IOL exchange, average post-operative refraction was 1.22D less myopic than predicted. This study confirms a hyperopic refractive shift when both IOLs and iris prostheses are placed into the capsular bag.

To assess relationship between dark without pressure (DWP) retinopathy and retinal vasculitis (RV) in paediatric uveitis patients. This is a retrospective cross-sectional study. Wide angle fundus photographs (WAFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT) images were analysed to identify DWP retinopathy. Confluent dark areas on WAFP, hypo-autofluorescence on FAF, and EZ disruption on OCT images were the markers for DWP. DWP retinopathy area was measured using Image-J. The prevalence and characteristics of DWP in RV patients and its association with RV was reported. Out of 43 paediatric uveitis patients, 26 were diagnosed with RV. Amongst these, DWP was detected in 20 patients (30 eyes) which were analysed. Mean age was 12.8 ± 3.36 years; 40% were female. DWP areas were either diffuse, mid-peripheral or peripheral on WAFP. All 20 patients (30 eyes) showed hypo-autofluorescence on FAF at the same locations as the WAFP. The mean duration of follow-up was 27.2 ( ± 13.7) months. 12 patients (19 eyes) who had DWP at baseline visit had longer duration of uveitis compared to 8 patients (11 eyes) who developed DWP on follow-up visits (p < 0.036). Progression of the retinopathy overtime was analysed in 28 eyes; all eyes showed improvement of RV with therapy. There was a statistically significant relationship between change in vascular leakage and the change in DWP retinopathy area (chi square= 11.67, p = 0.001). DWP can potentially serve as a biomarker of RV in paediatric uveitis patients and its presence should warrant WAFA evaluation in this patient population.

PurposeTo evaluate the safety and efficacy of subretinal gene therapy using AGTC-501 (rAAV2tYF-GRK1-RPGR) in male participants with X-linked retinitis pigmentosa (XLRP). DesignPhase 1/2, open-label, dose-escalation study. MethodsSetting: Four centers in the United States. Patient or Study Population: Twenty-nine males with XLRP and confirmed pathogenic RPGR variants. Mean age was 31.6 years (range 15-55). Intervention: Subretinal injection of AGTC-501 at doses ranging from 2.48 × 1010 to 1.99 × 1012 vg/eye administered in one eye per participant. Subretinal injection sites initially targeted the peripheral retina and then transitioned to the macula with successive cohorts. Main Outcome Measures: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), laboratory parameters, and immunological responses. Efficacy was evaluated by mesopic microperimetry mean sensitivity. ResultsAll 29 participants experienced ≥1 TEAE. Eleven (38%) experienced ≥1 grade 3 TEAE. Six (21%) experienced ≥1 ocular SAE related to AGTC-501, including retinal detachment (n=4), subcapsular cataract (n=1), and glaucoma (n=1). Two (6.9%) experienced non-ocular treatment-emergent SAEs. Immunological findings did not indicate safety concerns. Three of 4 participants at the highest dose exhibited concerning retinal pigment epithelial changes. Half the participants at the highest tolerated dose (6.8 × 1011vg/eye) maintained ≥7 dB improvement in ≥5 loci at 24 months. ConclusionsSubretinal AGTC-501 was generally well-tolerated. Despite all participants experiencing at least one TEAE, most of these events were mild in nature, exhibited complete resolution, and were associated with the subretinal injection procedure itself rather than the study agent. The highest dose exhibited an unfavorable risk-benefit profile due to the development of RPE changes. Although this group had the highest improvement in retinal sensitivity, our team has decided not to continue this dose in future clinical trials. Preliminary efficacy was observed at the maximum tolerated dose. Further studies are warranted to assess long-term safety and efficacy of AGTC-501 for XLRP treatment.

This study sought to determine the effect of donor preservation time and other donor tissue factors on the clinical outcomes of keratolimbal allograft (KLAL) transplantation. In this retrospective chart review of patients who underwent KLAL transplantation, electronic health records were reviewed for relevant patient ocular and surgical history. Donor tissue factors were collected from donor reports. The primary outcome measure was time to epithelialization. Exclusion criteria included prior ocular surface stem cell transplantation, loss to follow-up, missing data from medical records, indication for surgery other than limbal stem cell deficiency, and early removal of KLAL tissue. Regression analysis was performed to compare time to epithelialization and donor tissue factors. Subgroup analysis was performed using the Student t test to evaluate the impact of donor preservation time on time to epithelialization. A total of 154 eyes were identified of which 122 were included for analysis. The mean time to epithelialization was 55 days and median was 35 days. No donor tissue factors were found to affect total time to corneal epithelialization. Subgroup analysis comparing the effect of different total preservation times on time to epithelialization did not reveal any statistically significant associations. No relationship was found between time to donor tissue preservation and time to epithelialization after KLAL surgery. It appears that limbal stem cells can be safely stored for up to 9 days in corneal storage solution in hypothermic temperatures without clinical consequences.

Anterior stromal puncture is an inexpensive and widely used technique at the slit lamp to treat recurrent corneal erosions (RCE), common sequelae of corneal abrasions, trauma, and epithelial basement membrane dystrophies (EBMDs). The purpose of this study was to determine safety of a novel anterior stromal micropuncture device (termed a "plexitome") for use in the optical axis of the cornea. We performed an IRB-approved clinical pilot study on 45 patients with diverse corneal pathologies to determine the safety of the plexitome device and examined corneal healing responses clinically for a minimum of 30 days after treatment. Follow on efficacy data was collected for treated patients with RCE.Micropuncture treatment was performed either through loose epithelial tissue or after debridement using a cotton tip at the slit lamp. After "imprinting," patients were treated with topical medications including antibiotics, hypertonic saline/ointment, bandage contact lenses, and/or patching according to the treating physician's routine care for the condition. Micropuncture using the "plexitome" device did not create visible scars in the corneal stroma of the 45 patients treated and followed for at least 30 days. Photographic evidence of imprinting was seen at in 1 patient at 30 days. There were no significant adverse events associated with treatment. Micropuncture of the cornea using the "plexitome" device does not create optically evident anterior stromal scarring after treatment. Micropuncture using the device may be an effective way of treating RCE and other corneal manifestations of EBMD in the optical axis, which is not currently possible using standard anterior stromal puncture methods.

In subretinal gene therapy for inherited retinal diseases (IRDs), blebs may not propagate predictably in the direction of the injection cannula. We evaluated factors that influenced bleb propagation among various IRDs. Retrospective review of all subretinal gene therapy procedures performed by a single surgeon between September 2018 and March 2020 for various IRDs. Main outcome measures were directional bias of bleb propagation and intraoperative foveal detachment. Desired injection volumes and/or foveal treatment were successfully achieved in all 70 eyes of 46 patients with IRD regardless of IRD indication. Bullous foveal detachment was associated with retinotomy closer to the fovea, posterior bleb bias, and greater bleb volumes ( P < 0.01). Blebs biased anteriorly or posteriorly based on disease indication ( P = 0.04) and age ( P < 0.001). Retinotomy location ≤ 3.7 mm (approximately two disk diameters) from the fovea favored foveal detachment ( P < 0.001). Multiple retinotomies and blebs allowed greater surface area coverage in some eyes, but intersecting blebs did not propagate further. Bleb formation and propagation are predictable based on patient age, retinotomy location, disease indication, and how tangentially fluid is directed into the subretinal space.