AMALRIC TRIANGULAR SIGN AND CAROTID DOPPLER ULTRASONOGRAPHIC FINDINGS IN CENTRAL RETINAL ARTERY OCCLUSION.

PURPOSE: The aim of this study was to determine the incidence of the Amalric triangular sign (ATS) in patients with central retinal artery occlusion and investigate its association with visual function and carotid Doppler ultrasonography findings. METHODS: A retrospective chart review was conducted on 21 eyes from 21 patients with complete central retinal artery occlusion. Best-corrected visual acuity and carotid Doppler ultrasonography findings [peak systolic velocity, end-diastolic velocity, and resistance index (RI) = (PSV - EDV)/PSV] were investigated. RESULTS: Three patients (14%) exhibited the ATS. Best-corrected visual acuity at first visit was significantly worse in ATS-positive patients than in ATS-negative patients (P = 0.024). Doppler waveform analysis of the common carotid artery showed that ATS-positive patients had a significantly lower end-diastolic velocity [P = 0.009, median 10 (range 9-10) vs. 17 (13-24) m/second] and significantly higher resistance index [P = 0.021, median 0.80 (range 0.79-0.83) vs. 0.72 (0.66-0.82)] than did ATS-negative. CONCLUSION: The Amalric triangular sign was observed in three patients with central retinal artery occlusion, who showed worse best-corrected visual acuity at the first visit than did those without the ATS. Carotid Doppler ultrasonography revealed that ATS-positive patients had a significantly higher resistance index and lower end-diastolic velocity at the common carotid artery than did ATS-negative, indicating steno-occlusive changes in the internal carotid artery.

Urokinase-type plasminogen activator negatively regulates α-smooth muscle actin expression via Endo180 and the uPA receptor in corneal fibroblasts.

Corneal fibroblasts are embedded within an extracellular matrix composed largely of collagen type 1, proteoglycans, and other proteins in the corneal stroma, and their morphology and function are subject to continuous regulation by collagen. During wound healing and in various pathological conditions, corneal fibroblasts differentiate into myofibroblasts characterized by the expression of α-smooth muscle actin (α-SMA). Endo180, also known as urokinase-type plasminogen activator (uPA) receptor-associated protein (uPARAP), is a collagen receptor. Here we investigated whether targeting of Endo180 and the uPA receptor (uPAR) by uPA might play a role in the regulation of α-SMA expression by culturing corneal fibroblasts derived from uPA-deficient (uPA-/-) or wild-type (uPA+/+) mice in a collagen gel or on plastic. The expression of α-SMA was upregulated, the amounts of full-length Endo180 and uPAR were increased, and the levels of both transforming growth factor-ß (TGF-ß) expression and Smad3 phosphorylation were higher in uPA-/- corneal fibroblasts compared with uPA+/+ cells under the collagen gel culture condition. Antibodies to Endo180 inhibited these effects of uPA deficiency on α-SMA and TGF-ß expression, whereas a TGF-ß signaling inhibitor blocked the effects on Smad3 phosphorylation and α-SMA expression. Our results suggest that uPA deficiency might promote the interaction between collagen and Endo180 and thereby increase α-SMA expression in a manner dependent on TGF-ß signaling. Expression of α-SMA is thus negatively regulated by uPA through targeting of Endo180 and uPAR.

STRUCTURAL OUTCOME AFTER SURGERY FOR STAGE 5 RETINOPATHY OF PREMATURITY BASED ON THE NEW INTERNATIONAL CLASSIFICATION: ICROP 3.

PURPOSE: This study investigated the outcomes of vitrectomy for Stage 5 retinopathy of prematurity (ROP) based on the International Classification of Retinopathy of Prematurity third edition, in which Stage 5 ROP is divided into three subgroups. METHODS: Fifty-four eyes of 34 patients with Stage 5 ROP who underwent vitrectomy between 2004 and 2020 were retrospectively analyzed. Data including sex, gestational age and weight at birth, International Classification of Retinopathy of Prematurity 3 subcategories, perioperative use of intravitreal bevacizumab injection and laser photocoagulation, surgical procedure and complications, final retinal reattachment, and follow-up period were collected. RESULTS: Complete retinal reattachment was achieved in 16 eyes (88.9%) with Stage 5A and 13 eyes (39.4%) with Stage 5B ( P = 0.0003, Wilcoxon rank-sum test). Three patients with Stage 5C were considered inoperable. Postoperative anatomical failure was significantly associated with stage (Stage 5B vs. 5A; odds ratio, 17.986; 95% confidence interval, 3.712-148.502; P = 0.0001, multivariate logistic regression analysis). Intraoperative intravitreal bevacizumab was significantly associated with lower postoperative incidence of vitreous hemorrhage and glaucoma ( P = 0.041, chi-square test). CONCLUSION: Staging of preoperative anatomical features based on International Classification of Retinopathy of Prematurity 3 is a useful predictor for final anatomical success. Intraoperative intravitreal bevacizumab might reduce postoperative complication risks.

CHOROIDAL AMYLOID DEPOSITION: A Multicenter Study of Amyloid Lesions Identified in Late Indocyanine Green Angiography.

PURPOSE: To characterize choroidal amyloid angiopathy (CAA) using late-phase indocyanine green angiography (ICGA). METHODS: This was a multicenter retrospective observational case series on patients with transthyretin (ATTR) and AL amyloidosis who underwent ICGA. The timing of hyperfluorescence and longitudinal changes were analyzed. RESULTS: Thirty-two patients (27 with ATTR and 5 with AL) with mean age of 58.9 ± 17.4 years were included. Hyperfluorescent spots in the very late phases of ICGA, corresponding to CAA, were observed in 49 of 55 eyes (89%). The median time to maximal staining was 672 (95% confidence interval, 644-752) seconds, which was significantly later than the initial staining (503 [95% confidence interval, 447-521], P < 0.0001; Wilcoxon signed rank test). In seven patients with ATTR amyloidosis who underwent follow-up of ICGA, the CAA was stable in two patients and improved in five patients during treatment. However, 3 patients (43%) had worsening vitreous opacities in both eyes, and 4 patients (57%) developed secondary open-angle glaucoma. CONCLUSION: Most patients with amyloidosis were found to have CAA on ICGA. Up to 12.5 minutes is required for maximal ICG staining. Choroidal amyloid angiopathy improved in most patients with systemic treatment and may serve as a marker of systemic disease status.

Identification of Interphotoreceptor retinoid-binding protein in the Schisis cavity fluid of a patient with congenital X-linked Retinoschisis.

BACKGROUND: This case report describes the surgical outcome in a patient with congenital X-linked retinoschisis (CXLRS) and the results of proteomic analysis of surgically extracted samples from both vitreous and intraschisis cavities by mass spectrometry. CASE PRESENTATION: A 3-month-old boy presented with extensive retinoschisis involving macula and retinal periphery in both eyes. Genetic analysis confirmed retinoschisin 1 mutation (c.554C > T), and an electroretinogram showed significant reduction of b-wave and decreased cone and rod responses, which led to a diagnosis of CXLRS. By performing pars plana vitrectomy, including inner wall retinectomy, clear visual axes with stable retinal conditions and functional vision in both eyes were obtained during the 4 years of follow-up. Proteomic analysis of surgically retrieved fluid from the intraschisis cavity revealed a higher expression of interphotoreceptor retinoid-binding protein (IRBP) than that from the vitreous humor. However, both samples showed equal levels of albumin, transferrin, and pigment epithelium-derived factor. CONCLUSIONS: Cellular adhesive imperfection in CXLRS may cause IRBP diffusion from the interphotoreceptor matrix, resulting in the strong expression of IRBP in the intraschisis cavity. An impaired retinoid cycle caused by an absence of IRBP in the retina may potentially underlie the pathology of CXLRS.

ASSOCIATION BETWEEN CHOROIDAL CHARACTERISTICS AND SYSTEMIC SEVERITY IN AMYLOIDOSIS.

PURPOSE: This study aimed to describe the choroidal features of ocular amyloidosis using multimodal imaging, to correlate these findings with systemic involvement, and to propose a choroidal grading system. METHODS: Eleven patients with systemic amyloidosis were reviewed retrospectively. Each case was assigned a grade according to the severity of choroidal findings as determined by both enhanced depth imaging optical coherence tomography and indocyanine green angiography. The severity of systemic amyloidosis was then correlated with the choroidal involvement. RESULTS: On indocyanine green angiography, all patients exhibited hyperfluorescent spots in the late stage and were classified according to preexisting criteria. On enhanced depth imaging optical coherence tomography, hyperreflective foci were seen in the choriocapillaris and Sattler's layer in Grade 1, partial loss of Sattler's layer was additionally seen in Grade 2, and a dense hyperreflective Haller's layer was seen in Grade 3. Choroidal grading scores were significantly correlated with the systemic severity score (P = 0.0014, Pearson's correlation coefficient; ρ = 0.83). CONCLUSION: With ocular amyloidosis, evaluation of choroidal characteristics using multimodal imaging may serve as a biomarker for systemic involvement.

Impact of posterior vitreous detachment on contrast sensitivity in patients with multifocal intraocular lens.

PURPOSE: To investigate posterior vitreous detachment (PVD) and pars plana vitrectomy (PPV) effects on contrast sensitivity function (CSF) in patients with a multifocal intraocular lens (MfIOL). METHODS: This single-center prospective case-control study analyzed 27 patients with 43 consecutive eyes. Twenty patients with 36 consecutive eyes received MfIOL implantation with either ZLB00 or ZMB00. CSF was measured as the area under the log contrast sensitivity function (AULCSF) in the presence and absence of PVD (PVD+ group and PVD- group, respectively). Seven eyes associated with a symptomatic PVD and severe visual dissatisfaction after MfIOL implantation underwent PPV (symptomatic PVD+ group). CSF was measured prior to and after PPV. RESULTS: The mean AULCSF was significantly lower in the PVD+ group (1.5 ± 0.1) versus the PVD- group (1.7 ± 0.1, p < 0.0001). Major complaints in the symptomatic PVD+ group included floaters (n = 2) and blurry vision (n = 5). The preoperative AULCSF (1.4 ± 0.1) was significantly lower in the symptomatic PVD+ group versus the PVD- group (p < 0.0001) and PVD+ group (p = 0.02). The preoperative AULCSF in the symptomatic PVD+ group was significantly improved after PPV (1.4 vs. 1.7, respectively, p = 0.002). CONCLUSIONS: PVD significantly decreased CSF in patients with MfIOL. Patients with symptomatic PVD exhibited the greatest decrease in CSF, which was significantly improved after PPV. Measurement of CSF and careful assessment of PVD may be useful in determining the appropriateness of surgical intervention for improving visual performance and satisfaction in MfIOL patients with symptomatic PVD.

Sweeping technique for the removal of emulsified silicone oil droplets from the anterior surface of the iris using an ophthalmic absorption sponge.

PURPOSE: Silicone oil (SO) tamponade is frequently used in complex vitreoretinal surgeries, and SO migration into the anterior chamber can lead to complications such as glaucoma and corneal decompensation. A new technique is described for the efficient removal of emulsified SO droplets, which can adhere strongly to the anterior surface of the iris. METHODS: The tip of an ophthalmic absorption sponge was cut to an approximately 1x1 mm size. Using forceps, the sponge was inserted through a 25-gauge trocar, then through a corneal paracentesis, to gently scrape the surface of the iris to dislodge the adherent SO droplets, which were subsequently aspirated. RESULTS: This technique efficiently and effectively dislodged and mobilized most emulsified SO droplets, thereby allowing removal via aspiration using a vitrector. Two months after surgery, the retina remained attached, the intraocular pressure decreased from 18 mmHg to 15 mmHg, and there were no visible SO droplets in the anterior chamber. CONCLUSION: The sweeping technique is a safe and efficient method to dislodge, mobilize and aspirate emulsified SO droplets that are adherent to the anterior surface of the iris, thereby decreasing the risk of future SO-related complications.

Avascular Peripheral Retina in Infants.

Avascular peripheral retina in an infant is a common characteristic of numerous pediatric retinal vascular disorders and often presents a diagnostic challenge to the clinician. In this review, key features of each disease in the differential diagnosis, from retinopathy of prematurity, familial exudative vitreoretinopathy, Coats disease, incontinentia pigmenti, Norrie disease, and persistent fetal vasculature, to other rare hematologic conditions and telomere disorders, will be discussed by expert ophthalmologists in the field.

Optical coherence tomography findings of the peripheral retina in patients with congenital X-linked retinoschisis.

Introduction: Congenital X-linked retinoschisis (XLRS) presents as macular retinoschisis/degeneration in almost all patients and as peripheral retinoschisis in half the patients. Although the optical coherence tomography (OCT) findings of macular retinoschisis have been well investigated, those of peripheral retinoschisis have rarely been reported. This study aimed to report the ultra-widefield OCT findings of the peripheral retina in patients with XLRS. Methods: Medical records of 10 Japanese patients (19 eyes) with clinically and/or genetically diagnosed XLRS were retrospectively reviewed. Funduscopic, electroretinographic, and OCT findings were reviewed and evaluated. Some were also genetically evaluated for the RS1 gene. Results: OCT of the macula revealed schises and/or cystoid changes in the inner nuclear layer (INL) and outer nuclear layer. In contrast, OCT of the peripheral retina revealed schises and/or cystoid changes in the INL in eight eyes (44%), and/or splitting in the ganglion cell layer (GCL) in 10 (56%) of the 18 eyes with clear OCT images. No schisis or cystoid changes were found in the peripheral OCT images of eight eyes (44%). A 16-year-old boy presented with retinal splitting of the GCL and INL of the inferior retina, although he had no ophthalmoscopic peripheral retinoschisis. Genetic examinations were performed on three patients, all of whom had reported missense mutations in the RS1 gene. Conclusion: In XLRS, peripheral bullous retinoschisis results from GCL splitting in the retina. One of the 10 patients with XLRS showed intraretinal retinoschisis in the GCL in the inferior periphery, which was unremarkable on ophthalmoscopy (occult retinoschisis). Although both peripheral bullous retinoschisis and occult retinoschisis showed splitting/cystic changes in the GCL, further studies are needed to determine whether occult retinoschisis progresses to bullous retinoschisis.

Late Vitreoretinal Complications of Regressed Retinopathy of Prematurity: Retinal Break, Vitreous Hemorrhage, and Retinal Detachment.

PURPOSE: To investigate late vitreoretinal complications and visual outcomes in patients with regressed retinopathy of prematurity (ROP) with or without prior treatment. DESIGN: International, multicenter, noncomparative retrospective case series. PARTICIPANTS: We analyzed 264 eyes of 238 patients from 13 centers worldwide who developed vitreoretinal complications (retinal detachment [RD], vitreous hemorrhage [VH], or retinal break) ≥ 2 years after resolution of acute ROP. METHODS: Each participant was assigned to 1 of 3 groups (the RD, VH, and retinal break groups) according to their primary diagnosis. The average age at presentation, visual acuities, refractive error, axial length, gestational age, birth weight, acute ROP classification, prior treatments for acute ROP, postoperative visual acuity (VA), and concomitant eye conditions in the 3 groups were documented and compared. MAIN OUTCOME MEASURES: Clinical features and visual outcomes of late vitreoretinal complications in patients with regressed ROP. RESULTS: A total of 264 eyes of 238 patients were included. The prior acute ROP status was comparable among the 3 groups, except that the VH group had a higher proportion of patients with type 1 ROP (P = 0.03) and prior treatment (P < 0.001) than the other groups. The average age at presentation was earlier in the RD (20.3 ± 15.5 years) and VH (21.4 ± 18.9 years) groups than in the retinal break group (31.9 ± 18.2 years; P < 0.001). The retinal break group had the best presenting best-corrected VA, followed by the RD and VH groups (P < 0.001). Surgical intervention improved VA in both the RD and VH groups (both P < 0.05). The overall trend of VA was the most favorable in the retinal break group, followed by that in the VH and RD groups. Cicatricial changes in the fellow retina were observed in > 90% of patients with unilateral involvement. CONCLUSIONS: Infants with acute ROP remain at a high risk of vision-threatening complications throughout childhood and adulthood. Continual follow-up of patients with ROP is important. When severe complications, such as RD or VH, are detected, timely surgical intervention is necessary to ensure favorable visual outcomes in these patients.

Methodological Approach to Improve Surgical Outcomes of a Pig Subretinal Implantation Model.

Purpose: To improve outcomes for subretinal implantation surgery in pigs. Methods: Analysis of variables affecting the success of subretinal implantation surgery was performed on videos of 37 surgeries. Ex vivo experiments were conducted to measure intraocular pressure (IOP) and test various prototyped implanters for effectiveness at maintaining IOP. Results: A video analysis revealed a prolonged sclerotomy open time owing to a combination of uncontrolled bleeding and excessive fluid outflow often resulting in retinal prolapse. Precauterization of the choroid before full-thickness sclerotomy (n = 10) resulted in a reduced incidence of uncontrolled bleeding from 39.1% (9/23) versus 0% (0/10) (P = 0.005) and improved implantation success from 73% to 90%. An ex vivo analysis of the IOP revealed a mean decrease in the IOP from 30.2 ± 3.0 mm Hg to 5.0 ± 2.1 mm Hg after a fully penetrating sclerotomy. To address this situation, we produced a series of plugs that integrated with a custom implant insertion device to seal the sclerotomy during implantation. The use of the plugs was cumbersome, however, and so we opted instead to increase the width of the inserter tip to fill the open sclerotomy. This improved device restored and maintained IOP during implantation (27.1 ± 1.9 mm Hg). Combined with precauterization the improved inserter resulted in 100% successful implantation (n = 4). Conclusions: For subretinal implantation in pigs, a modified procedure to precauterize the choroid before sclerotomy combined with an instrument that better fills the scleral opening decreases bleeding, hypotony, and open sclerotomy time, improving the success rate. Translational Relevance: Better management of IOP and bleeding from a sclerotomy will improve implant-based therapies.

Association of Drusen Phenotype in Age-Related Macular Degeneration from Human Eye-Bank Eyes to Disease Stage and Cause of Death.

PURPOSE: To stage maculopathy, assess and quantify drusen, determine drusen subtype frequency, and compare subtypes with age-related macular degeneration (AMD) stage and cause of death using an eye-bank model of AMD. DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand ninety-two human eyes from 1067 eye-bank donors, selected from a population at risk for AMD. METHODS: We analyzed donor eye tissue images (2005-2020) using both the 4- and 9-step Minnesota Grading System (MGS), an AMD grading system for eye-bank eyes corresponding to the Age-Related Eye Disease Study classification. The 9-step MGS quantifies total drusen area, hyperpigmentation, and depigmentation. We analyzed reticular pseudodrusen (RPD), basal laminar drusen (BLD), and calcified drusen (CaD) frequency within this population and explored associations with AMD stage, donor age, gender, and cause of death. Statistical analyses were performed using Wilcoxon rank-sum and chi-square tests. Testing encompassed staging eye-bank eyes using MGS analysis. MAIN OUTCOME MEASURES: Drusen subtype frequency associations with AMD stage and cause of death. RESULTS: We detected RPD in 228 (13%), BLD in 131 (7%), and CaD in 84 (5%) of the examined eyes (n = 1777). All subtypes were associated with advanced AMD (RPD: odds ratio [OR], 3.4 [95% confidence interval (CI), 2.5-4.5; P < 0.0001]; BLD: OR, 2.2 [95% CI, 1.5-3.2; P < 0.0001]; and CaD: OR, 39.1 [95% CI, 16.8-91.0; P < 0.0001]). Only the RPD subtype was associated statistically with cardiovascular death when compared with those without cardiovascular death (48% vs. 32%; OR, 2.0 [95% CI, 1.4-2.9]; P = 0.0002). CONCLUSIONS: In a large group of eye-bank eyes selected from a population at risk for AMD and graded using the 4-step and 9-step MGS, RPD, BLD, and especially CaD were associated strongly with advanced AMD. The RPD subtype was associated with a cardiovascular cause of death and may represent an ophthalmologic biomarker for cardiovascular disease.

Effects of Zinc Acetate Hydrate Treatment on Serum Oxidative Stress Markers in Patients with Macular Drusen.

Purpose: To measure the serum levels of the oxidative stress markers superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) and compare them before and after zinc supplementation in patients with early age-related macular degeneration (AMD). Methods: We measured serum zinc levels in 65 patients with early AMD. Of these, 29 patients with macular drusen and a serum zinc level <80 µg/dL received oral zinc acetate dihydrate (50 mg/day). Serum trace metal levels (zinc and copper) and oxidative stress marker levels (SOD, MDA, and GPx) were measured at baseline and 12 weeks after the treatment. The macular drusen areas and best-corrected visual acuity were evaluated in 24 participants who attended the 3-month follow-up. Results: MDA level was significantly decreased from baseline to 12 weeks after zinc administration (170.5 ± 100.9 vs. 148.3 ± 57.9 pmol/mL, P = 0.03), while SOD was significantly increased from baseline to 12 weeks after zinc intake (4.2 ± 0.9 vs. 4.6 ± 0.9 U/mL, P = 0.03). The serum zinc level was significantly correlated with the MDA level (P = 0.03, ρ = -0.26). The area of soft drusen was significantly decreased after zinc treatment (1,936,654.9 ± 1,348,267.6 vs. 966,883.9 ± 719,938.1 µmm2, P = 0.04). Conclusions: The levels of oxidative stress markers MDA and SOD decreased and increased, respectively, after oral zinc administration to 24 patients with AMD. The therapeutic effect of zinc treatment on drusen area might differ depending on the drusen phenotype in early AMD.

Vitrectomy and external drainage of subretinal fluid containing high concentration of vascular endothelial growth factor for advanced coats disease.

This study investigated the surgical outcomes of Coats disease and the role of external drainage (XD) of subretinal fluid (SRF). The study is a multicenter retrospective interventional case series of 26 consecutive eyes of 26 patients who underwent surgeries for advanced Coats disease with retinal detachment. Main outcomes measured were: 1) comparison of complete SRF resolution with or without XD, and 2) variables that were associated with functional postoperative best-corrected visual acuity (BCVA) defined as BCVA of 0.1 or better, 3) intraocular vascular endothelial growth factor (VEGF) levels. Complete SRF resolution was achieved in all 14 eyes in which XD had been performed and in 75% of 12 eyes in which XD had not been performed (P = .03). Multivariable logistic regression analysis revealed that initial BCVA was the only variable associated with functional postoperative BCVA (odds ratio 3.24, 95% CI 0.93-11.33; P = .04). Markedly elevated VEGF levels were noted in the SRF compared with those in the vitreous humor (49,760 ± 52,990 vs. 707 ± 611 pg/mL, P = .03). XD seems to provide better anatomical success than without XD in the treatment of advanced Coats disease as XD could effectively eliminate substantial amount of VEGF in the SRF.

Drug Tissue Distribution of TUDCA From a Biodegradable Suprachoroidal Implant versus Intravitreal or Systemic Delivery in the Pig Model.

Purpose: To determine local ocular tissue levels of the bile acid, tauroursodeoxycholic acid (TUDCA), in the pig model using oral, intravenous (IV), intravitreal injection (IVitI) and low- and high-dose suprachoroidal, sustained-release implants (SCI-L or SCI-H). Methods: Forty-six pigs (92 globes) were included in the study. TUDCA was delivered orally in 5 pigs, IV in 4, IVitI in 6, SCI-L in 17, and SCI-H in 14. Testing timeframes varied from the same day (within minutes) for IV; 1 to 6 days, oral; and 1 to 4 weeks, IVitI and SCI. Enucleated globes were dissected, specimens from specific tissues were separated, and TUDCA was extracted and quantified using mass spectrometry. Results: The highest TUDCA tissue levels occurred after IV delivery in the macula (252 ± 238 nM) and peripheral retina (196 ± 171 nM). Macular choroid and peripheral choroid levels were also high (1032 ± 1269 and 1219 ± 1486 nM, respectively). For IVitI delivery, macular levels at day 6 were low (0.5 ± 0.5 nM), whereas peripheral choroid was higher (15.3 ± 16.7 nM). Neither the SCI-L nor SCI-H implants delivered meaningful macular doses (≤1 nM); however, peripheral retina and choroid levels were significantly higher. Bile acid isoforms were found in the serum specimens. Conclusions: The highest TUDCA tissue levels in the pig model were obtained using IV delivery. Oral delivery was associated with reasonable tissue levels. Local delivery (IVitI and SCI) was able to achieve measurable local ocular tissue levels. Translational Relevance: Diffusional kinetics from the suprachoroidal space follow the choroidal blood flow, away from the macula and toward the periphery.

Fibrin hydrogels are safe, degradable scaffolds for sub-retinal implantation.

Retinal pigment epithelium (RPE) transplantation for the treatment of macular degeneration has been studied for over 30 years. Human clinical trials have demonstrated that RPE monolayers exhibit improved cellular engraftment and survival compared to single cell suspensions. The use of a scaffold facilitates implantation of a flat, wrinkle-free, precisely placed monolayer. Scaffolds currently being investigated in human clinical trials are non-degradable which results in the introduction of a chronic foreign body. To improve RPE transplant technology, a degradable scaffold would be desirable. Using human fibrin, we have generated scaffolds that support the growth of an RPE monolayer in vitro. To determine whether these scaffolds are degraded in vivo, we developed a surgical approach that delivers a fibrin hydrogel implant to the sub-retinal space of the pig eye and determined whether and how fast they degraded. Using standard ophthalmic imaging techniques, the fibrin scaffolds were completely degraded by postoperative week 8 in 5 of 6 animals. Postmortem histologic analysis confirmed the absence of the scaffold from the subretinal space at 8 weeks, and demonstrated the reattachment of the neurosensory retina and a normal RPE-photoreceptor interface. When mechanical debridement of a region of native RPE was performed during implantation surgery degradation was accelerated and scaffolds were undetectable by 4 weeks. These data represent the first in situ demonstration of a fully biodegradable scaffold for use in the implantation of RPE and other cell types for treatment of macular degeneration and other retinal degenerative diseases.

Recurrent herpes zoster ophthalmicus in a young, healthy individual taking high doses of l-Arginine.

PURPOSE: To report a case of a healthy, young male with recurrent herpes zoster ophthalmicus (HZO) and high-dose l-arginine supplementation. OBSERVATIONS: A 39-year-old man presented to another institution with a HZO involving the right eye. He was treated with oral acyclovir with complete resolution. Four months later the patient had a recurrent HZO episode and was started again on oral acyclovir. After resolution of the episode, the patient was continued on 1 g of oral acyclovir daily as a prophylactic measure. He then presented to our institution for a second opinion. The patient was otherwise healthy, with no past medical history involving systemic immunosuppressant agents or HIV. However, the patient was an active weight lifter taking high doses of amino acids. A diet recall was performed prior to both HZO episodes, which calculated an average intake of 46.5 g of l-arginine a day. Examination revealed 20/40 best-corrected acuity, anterior stromal haze in the visual axis, and inferior superficial punctate keratitis in the right eye. The patient was treated for dry eye disease with punctual plugs and artificial tears. The patient was instructed to decrease all supplemental arginine consumption while continuing with oral acyclovir prophylaxis for one year. CONCLUSIONS AND IMPORTANCE: l-arginine is associated with the replication and virulence of a variety of viruses in vitro, including herpes simplex and varicella zoster. Although arginine consumption increased prior to the initial and recurrent HZO infection, further investigation needs to be performed to deem if a true association exists.

Repair of Traumatic Rhegmatogenous Retinal Detachment Combined with Congenital Falciform Retinal Detachment.

PURPOSE: To report a case of surgical repair of traumatic rhegmatogenous retinal detachment combined with congenital falciform retinal detachment (FRD). METHODS: A retrospective case report. RESULTS: A 36-year-old man with traumatic rhegmatogenous retinal detachment complicating a previously known FRD was successfully treated despite residual FRD following pars plana lensectomy, vitrectomy, and encircling scleral buckling. His best corrected visual acuity improved from hand motion at 50 cm to 20/1,000. CONCLUSION: We concluded that the root of the FRD is susceptible to trauma because of the contraction of fibrovascular tissue. The early intervention of modern vitrectomy to traumatic rhegmatogenous retinal detachment complicating a previously known FRD is an important consideration for enhanced quality of care and optimal patient outcomes.

Unilateral Multifocal Intraocular Lens Implantation in a Patient with Adie's Pupil.

PURPOSE: To report a case of a patient with unilateral Adie's pupil who underwent bilateral cataract extraction with multifocal and monofocal posterior chamber intraocular lens (IOL) implantation. METHODS: A 74-year-old woman presented to our institution complaining of worsening near vision. Gross examination revealed a 6-mm fixed pupil on the right eye (OD) and a 5-mm pupil reacting to 3 mm with light on the left eye (OS). Slit lamp examination revealed a tonic pupil with an exaggerated pupillary constriction to dilute pilocarpine OD. Dilated exam revealed 2-3+ nuclear and cortical lens changes bilaterally. The patient's active lifestyle, personality, and biometry measurements made her a good candidate for multifocal IOL (MfIOL) implantation OS. Femtosecond laser-assisted cataract extraction with a ReSTOR +3 ADD (SN60D1) implantation was performed OS. Monofocal lens implantation (SN60WF) was performed OD 6 months later. RESULTS: One year postoperatively, our patient had an uncorrected visual acuity (VAsc) of 20/15 for distance and J10 for near OD. Her VAsc was 20/25 +1 for distance and J1 for near OS. Visual acuity when using both eyes was 20/15 for distance and J1 for near. CONCLUSION: Optimizing success for MfIOL implantation is a multifactorial process. Large pupils preoperatively are of particular concern, as this may lead to increased dysphotopsia with pupil-dependent MfIOLs. Thus, patients with unilateral mydriasis, such as Aide's pupil, may have a beneficial outcome combining multifocal-monofocal implantation after bilateral cataract extraction, especially if they are not a candidate for monovision but desire spectacle independence.