Intravitreal quantum dots for retinitis pigmentosa: a first-in-human safety study.

Background: Studies indicate that electrical stimulation of retinitis pigmentosa (RP) retina is beneficial. Quantum dots (QDs) can convert light to electrical stimulus and therefore may have therapeutic potential for RP. Methods: This was an open-label, fellow eye-controlled, first-in-human safety study. Five adults with end-stage (arm A) and 15 with severe (arm B) RP received one or two intravitreal injections of 0.2 or 2µM cadmium/selenium 655 Alt QDs. Results: No adverse events were attributed to QDs. In arm A, median best corrected visual acuity was unchanged. In arm B, mean best corrected visual acuity improved from 6/398 to 6/177, versus 6/147 to 6/144 in the fellow eye. Conclusion: Intravitreal QDs can be safely administered to patients with RP. Vision appears to benefit and further validating studies are justified.

Lay abstract This study investigated the use of quantum dots (QDs) to treat very advanced retinitis pigmentosa (RP), a disease characterized by progressive loss of peripheral and then central vision. QDs are sometimes called 'artificial atoms'. If they are injected into the eye, they settle in the retina, the light-sensing layer of cells that is damaged by RP. When light enters the eye, it is absorbed by the QDs in the retina, and the light energy is converted to electrical energy. Electrical stimulation has been shown to benefit degenerating retina, as occurs in RP, and hence QDs may have the potential to improve or preserve vision in people with RP. This preliminary study recruited 20 people with very severe RP and injected QDs into their eyes. We aimed to see whether the QDs were safe. No adverse reactions were attributed to the QDs, and the average vision of treated eyes improved, whereas the participants' untreated fellow eyes showed no real change in vision. Although encouraging, these results are only preliminary, and a larger study is planned to explore these findings.

Intraoperative fibrin formation during Descemet membrane endothelial keratoplasty.

PURPOSE: To describe Descemet membrane endothelial keratoplasty (DMEK) cases complicated by spontaneous intraoperative fibrin formation. METHODS: DMEK surgeries performed at two centers using a standardized technique were reviewed retrospectively for the occurrence of intraoperative fibrin formation. Cases were assessed for recipient medical history, donor age, best spectacle-corrected visual acuity (BSCVA), intraoperative unscrolling time, 6-month endothelial cell loss (ECL), and the course of the mate donor cornea. RESULTS: In this review of 868 cases of standardized DMEK surgery with surgical peripheral iridotomy, 32 eyes of 29 patients (3.7%) were complicated by the formation of intraoperative fibrin formation, including 3 patients that developed fibrin in both eyes. Three of the 32 grafts failed (9.4%). None of the mate corneas transplanted (n = 27) developed complications related to fibrin. The donor age ranged from 51 to 75 years and recipient age ranged from 49 to 82 years (median, 66 years). Unscrolling time ranged from 1 to 105 min (median, 15 min). Nine eyes required one rebubble procedure. No eyes had vision-limiting comorbidities, and the 6-month BSCVA was ≥20/40 in all eyes. Six-month ECL ranged from 19% to 73% (median, 44%). CONCLUSIONS: We conclude that fibrin formation during DMEK surgery is an uncommon but important complication that can make graft manipulation more difficult, and may have deleterious effects on endothelial cell density and graft survival.

DMEK outcomes using nondiabetic grafts for recipients with diabetes mellitus.

PURPOSE: To compare Descemet membrane endothelial keratoplasty (DMEK) outcomes using nondiabetic grafts in diabetic and nondiabetic recipients. METHODS: All eyes that underwent DMEK between February 2013 and October 2016 (follow-up ≥3 months, without prior keratoplasty) were included. Recipients were divided into diabetic (insulin dependent [IDDM] or noninsulin dependent [NIDDM]) and nondiabetic groups. Main outcome measures included postoperative visual acuity, rebubble procedure rates, and graft failure rates. RESULTS: Of 334 eyes (243 subjects) included for analysis, 63 eyes (18.8%) were from diabetic recipients. At each timepoint, best-corrected visual acuity trended lower for IDDM recipients compared to NIDDM and nondiabetic recipients. There were no statistically significant differences in rebubble rates of diabetic compared to nondiabetic recipients (20.6% vs. 12.9%, p = 0.17), or IDDM compared to nondiabetic recipients (27.3% vs. 12.9%, p = 0.08; hazard ratio 2.26). Overall, 13 grafts (3.9%) failed (mean follow-up, 565 days; range, 90-1293 days). Graft failures did not differ between diabetic and nondiabetic recipients (4.0% vs. 4.9%, p = 0.15) regardless of subgroup (p = 0.36). CONCLUSIONS: DMEK provides excellent outcomes for patients with and without diabetes. DMEK outcomes were excellent with improvements in visual acuity and low rates of graft failure. Our findings were unable to determine differences between rebubble procedure rates but do emphasize the need for further research using stratified groups based on diabetes severity.

Evaluation of interferon alpha 2b as adjunctive therapy for conjunctival melanoma.

PURPOSE: Interferon alpha 2b (IFN-α2b) has been used as an adjunctive agent to treat conjunctival melanoma (CM), however its efficacy is unproved due to a paucity of data. We present 5 cases of incompletely excised CM lesions to inform clinical decision making regarding the adjunctive use of IFN-α2b. OBSERVATIONS: We identified all biopsy proven CM cases treated between 1997 and 2017 at the University of Iowa. Of these, we analyzed cases in which topical IFN-α2b drops were prescribed after the initial excision to treat surgical margins that were positive for primary acquired melanosis [PAM] with or without atypia or invasive CM. We noted the origin of CM (nevus, PAM, or de novo), presence and location of margins positive for residual melanoma, duration of IFN-α2b treatment, recurrences, time to recurrence, and outcome at last follow-up. Topical IFN-α2b drops (1 million IU/mL 4 times daily for 3-6 months) were used as adjunctive therapy in 5 cases following incomplete surgical excision of CM. The preceding lesion was PAM in 4 cases and compound nevus in 1 case. In 2 cases, margins were positive for PAM with atypia and both resulted in remission of melanoma at 54 and 33 months, respectively. However, in 3 cases, margins were positive for invasive melanoma and all 3 developed recurrence of melanoma despite IFN-α2b use. CONCLUSIONS AND IMPORTANCE: There are limited data regarding the efficacy of IFN-α2b as adjunctive therapy for incomplete excision of CM lesions. In this series, adjunctive topical IFN-α2b did not prevent recurrence in cases with surgical margins positive for invasive melanoma. Our results indicate that caution should be exercised when considering adjunctive IFN-α2b to treat CM lesions not excised completely.

Uveal Melanoma with Histopathologic Intratumoral Heterogeneity Associated with Gene Expression Profile Discordance.

PURPOSE: To report a case of intratumoral gene expression profile discordance in a malignant uveal melanoma, associated with intratumoral heterogeneity based upon histopathologic features. METHODS: The clinical history, fundus findings, imaging and histopathologic features, and DecisionDx-UM gene expression profile results (Castle Biosciences, Inc., Phoenix, AZ, USA) of the tumor were reviewed. RESULTS: A trans-retinal fine-needle aspiration biopsy was performed for a thin, pigmented choroidal tumor in a 33-year-old man. Cells obtained from this biopsy were tested using the DecisionDx-UM gene expression profile test and the tumor was classified as class 1A. Cytology confirmed melanoma. The patient subsequently elected to undergo enucleation. On microscopic examination of the globe, the tumor was composed primarily of spindle B cells, but had a focal area composed of epithelioid cells. This portion of the tumor was subsequently tested and demonstrated a class 1B gene expression profile. CONCLUSION: Intratumoral discordance in gene expression profile results has been described in uveal melanomas. Here we demonstrate that this discordance may be associated in some cases with intratumoral heterogeneity based upon histopathologic features.

Vaccine-Associated Uveitis.

All of the widely administered vaccines have been reported to cause uveitis. The ocular inflammation is usually temporary and resolves with topical ocular steroids. During a 26-year period, a total of 289 cases of vaccine-associated uveitis were reported to three adverse reaction reporting databases. Hepatitis B vaccine, either alone or administered with other vaccines, appears to be the leading offender. Clinicians are encouraged to report cases of vaccine- or drug-associated ocular adverse reactions to www.eyedrugregistry.com.

An assessment of antenatal care among Syrian refugees in Lebanon.

BACKGROUND: After more than three years of violence in Syria, Lebanon hosts over one million Syrian refugees creating significant public health concerns. Antenatal care delivery to tens of thousands of pregnant Syrian refugee women is critical to preventing maternal and fetal mortality but is not well characterized given the multiple factors obtaining health data in a displaced population. This study describes antenatal care access, the scope of existing antenatal care, and antenatal and family planning behaviors and practice among pregnant Syrian refugees in various living conditions and multiple geographic areas of Lebanon. METHODS: A field-based survey was conducted between July and October 2013 in 14 main geographic sites of refugee concentration. The assessment evaluated antenatal services among a non-randomized sample of 420 self-identified pregnant Syrian refugee women that included demographics, gestational age, living accommodation, antenatal care coverage, antenatal care content, antenatal health behaviors, antenatal health literacy, and family planning perception and practices. RESULTS: In total, 420 pregnant Syrian refugees living in Lebanon completed the survey. Of these, 82.9% (348) received some antenatal care. Of those with at least one antenatal visit, 222 (63.8%) received care attended by a skilled professional three or more times, 111 (31.9%) 1-2 times, and 15 (4.3%) had never received skilled antenatal care. We assessed antenatal care content defined by blood pressure measurement, and urine and blood sample analyses. Of those who had received any antenatal care, only 31.2% received all three interventions, 18.2% received two out of three, 32.1% received one out of three, and 18.5% received no interventions. Only (41.2%) had an adequate diet of vitamins, minerals, and folic acid. Access, content and health behaviors varied by gestational age, type of accommodation and location in Lebanon. CONCLUSIONS: Standards of antenatal care are not being met for pregnant Syrian refugee women in Lebanon. This descriptive analysis of relative frequencies suggests reproductive health providers should focus attention on increasing antenatal care visits, particularly to third trimester and late gestational age patients and to those in less secure sheltering arrangements. With this approach they can improve care content by providing early testing and interventions per accepted guidelines designed to improve pregnancy outcomes.