OUTCOMES OF INFECTIOUS PANUVEITIS ASSOCIATED WITH SIMULTANEOUS MULTI-POSITIVE OCULAR FLUID POLYMERASE CHAIN REACTION.

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling. METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021. RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n = 6, 21.4%), and Toxocara (n = 1, 3.6%). Mean initial and final visual acuity (logarithm of the minimum angle of resolution) were 1.3 ± 0.9 (Snellen ∼20/400) and 1.3 ± 1.1 (Snellen ∼20/400), respectively. Cytomegalovirus-positive eyes (n = 16, 61.5%) had a mean final visual acuity of 0.94 ± 1.1 (Snellen ∼20/175), whereas cytomegalovirus-negative eyes (n = 10, 38%) had a final visual acuity of 1.82 ± 1.0 (Snellen ∼20/1,320) ( P < 0.05). Main clinical features included intraocular inflammation (100%), retinal whitening (84.6%), immunosuppression (65.4%), retinal hemorrhage (38.5%), and retinal detachment (34.6%). CONCLUSION: Cytomegalovirus or Epstein-Barr virus were common unique pathogens identified in multi-PCR-positive samples. Most patients with co-infection were immunosuppressed with a high rate of retinal detachment and poor final visual acuity. Cytomegalovirus-positive eyes had better visual outcomes compared with cytomegalovirus-negative eyes.

INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. METHODS: A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed. RESULTS: There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination. CONCLUSION: Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.

Suprachoroidal Injection of Triamcinolone Acetonide Injectable Suspension for the Treatment of Macular Edema Associated With Uveitis in the United States: A Cost-Effectiveness Analysis.

OBJECTIVES: Suprachoroidal injection of triamcinolone acetonide is the first Food and Drug Administration-approved treatment for macular edema associated with uveitis. A cost-effectiveness analysis was performed comparing this treatment with best supportive care (BSC) for the management of this indication from US Medicare and commercial payer perspectives. METHODS: A patient-level simulation was developed per the patient characteristics and changes in best-corrected visual acuity letter scores observed in a phase III study of triamcinolone acetonide (PEACHTREE). The wholesale acquisition cost of triamcinolone acetonide was $1650/injection; suprachoroidal injection cost was assumed at $200/injection. Healthcare costs were informed by a US claims-based analysis. Mortality risk associated with severe vision loss and blindness was modeled by applying a hazard ratio to all-cause mortality rates of the US general population. Health-related quality of life weights, obtained from a regression model fitted to the Visual Function Questionnaire-25 data from PEACHTREE, were applied based on the best-corrected visual acuity scores of both eyes. Costs (2020 US dollar) and benefits were discounted at 3% annually. Incremental cost-effectiveness ratios were estimated over a 10-year horizon. RESULTS: In the base-case, the incremental cost-effectiveness ratio comparing triamcinolone acetonide with BSC was $28 479 per quality-adjusted life-year gained. The wholesale acquisition cost for triamcinolone acetonide for suprachoroidal use was ∼68%, ∼56%, and ∼27% below the willingness-to-pay thresholds of $150 000, $100 000, and $50 000 per quality-adjusted life-year gained, respectively. Results were robust in sensitivity and scenario analyses. CONCLUSIONS: Triamcinolone acetonide for suprachoroidal use is cost-effective compared with BSC for patients with macular edema associated with uveitis.

Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.

PURPOSE: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328). PARTICIPANTS: Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes). METHODS: The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group. MAIN OUTCOME MEASURES: Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset. RESULTS: Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%. CONCLUSIONS: This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.

Drug-related adverse effects of antivascular endothelial growth factor agents.

PURPOSE OF REVIEW: Antivascular endothelial growth factor (VEGF) agents have provided historic therapeutic breakthroughs in the treatment of retinal disease. New anti-VEGF agents are emerging for the treatment of retinal vascular diseases. Both systemic and ocular adverse effect need to be understood in managing patients. This review aims to highlight the adverse effects seen with routine use of bevacizumab, ranibizumab and aflibercept, as well as with new medications such as brolucizumab and abicipar. RECENT FINDINGS: We review the recent findings of intraocular inflammation (IOI) of brolucizumab and abicipar in the context of the efficacy and safety reported with the routine anti-VEGF agents. Specifically, brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of IOI, which has not been seen in other anti-VEGF medications. In addition, abicipar appears to cause IOI at a higher rate of patients than other anti-VEGF agents have previously. SUMMARY: Newer anti-VEGF agents pose a significant risk of adverse events not seen with routine anti-VEGF agents.

Vision Loss after Intravitreal Injection of Autologous "Stem Cells" for AMD.

Adipose tissue-derived "stem cells" have been increasingly used by "stem-cell clinics" in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue-derived "stem cells" at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients' severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients' visual acuity ranged from 20/200 to no light perception.

Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

PURPOSE: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Fifteen eyes from 12 patients identified from 10 United States centers. METHODS: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings. MAIN OUTCOME MEASURES: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies. RESULTS: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033). CONCLUSIONS: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.

Assessing "Cell Therapy" Clinics Offering Treatments of Ocular Conditions using Direct-to-Consumer Marketing Websites in the United States.

PURPOSE: "Cell therapy" is becoming increasingly available to the public via online direct-to-consumer advertisement within the United States (U.S.). The current study investigates the scope of "cell therapy" clinics across the U.S. that advertise and offer "cell therapy" for ocular conditions based on information provided on their websites. DESIGN: Cross-sectional study. PARTICIPANTS: The study included companies that are U.S.-based, participate in direct-to-consumer online marketing, have websites that can be data-mined with content analysis, and advertise therapy for ocular conditions. METHODS: Using a systematic, extensive keyword-based Internet search, content analysis of company websites was utilized to identify, document, and analyze U.S. businesses marketing "cell therapy" for ocular conditions as of September 16, 2017. MAIN OUTCOME MEASURES: Clinic locations, source of stem cells used, route of administration, marketed ocular conditions, and cost of treatment. RESULTS: Forty companies with 76 clinics use "cell therapy" to treat ocular conditions. California (23), Florida (12), and Illinois (10) contain the most clinics. All 40 companies specified sources of cells, which included autologous adipose-derived stem cells (35; 67%), autologous bone marrow-derived stem cells (8; 15%), amniotic stem cells (2; 4%), peripheral blood-derived stem cells (2; 4%), umbilical cord blood stem cells (2; 4%), allogenic bone marrow-derived stem cells (1; 2%), placental stem cells (1; 2%), and xenocells (1; 2%). The most commonly marketed ocular conditions included macular degeneration (35), optic neuritis (18), retinitis pigmentosa (17), and diabetic retinopathy (16). The most common routes of administration were intravenous (22) and "unspecified" (12); however, other companies listed more ocular-specific routes such as intravitreal injections (2), retrobulbar injections (2), eye injections (2), retrofundal injection (1), sub-Tenon injection (1), intraocular injection with vitrectomy (1), and eye drops (1). The cost of advertised "cell therapy" ranged from $4000 to $10 500. CONCLUSIONS: "Cell therapy" for ocular conditions is readily available via direct-to-consumer marketing strategies across the United States. The "cells" are harvested from numerous sources and administered through different methods for multiple ocular conditions at these "cell therapy" clinics. Limited data for these treatments necessitates advocating caution to physicians and patients about treatments offered at commercial "cell therapy" clinics.

OUTCOMES OF PARS PLANA VITRECTOMY FOR MACULAR HOLE IN PATIENTS WITH UVEITIS.

PURPOSE: Inflammatory macular hole is a rare complication of uveitis, and data on surgical outcomes of closure are scarce. The purpose of this study is to evaluate the anatomical and visual outcomes of conventional pars plana vitrectomy for patients with uveitis. METHODS: Noncomparative, interventional, and consecutive case series from 6 vitreoretinal surgical centers from 2007 to 2015. Twenty eyes of 19 patients were included with 4 patients separated as viral retinitis. The primary outcome was change in best-corrected visual acuity at Month 3. Secondary outcomes were closure of the macular hole and postoperative optical coherence tomography characteristics. RESULTS: All eyes underwent conventional three-port pars plana vitrectomy with indocyanine green-assisted internal limiting membrane peeling. Mean Snellen best-corrected visual acuity improved from 20/200 to 20/63 (P = 0.01 for a difference in logarithm of the minimum angle of resolution) at Month 3. Twelve (75%) of patients achieved 2 or more lines of visual acuity improvement by postoperative Month 3. Surgery resulted in decreased epiretinal membrane (P = 0.002), intraretinal fluid (P < 0.001), subretinal fluid (P = 0.029), central subfield thickness (P < 0.001), and central cube volume (P = 0.041). Surgical intervention achieved anatomical success, as measured by macular hole closure, in 13 (81%) of patients at postoperative Month 3. CONCLUSION: Patients with inflammatory macular hole respond well to conventional surgery, with good anatomical and visual acuity outcomes.

Impact of Total Pars Plana Vitrectomy on Postoperative Complications in Aphakic, Snap-On, Type 1 Boston Keratoprosthesis.

PURPOSE: To determine the impact of total pars plana vitrectomies (PPVs) with peripheral shaving of the vitreous base on the rates of postoperative complications in patients with aphakic, snap-on type I Boston keratoprostheses (KPros). DESIGN: Retrospective, consecutive case series. PARTICIPANTS: A total of 48 eyes in 46 patients with implantation of aphakic, snap-on type 1 Boston KPros performed at a tertiary care facility between January 1, 2007, and December 31, 2013, were included. METHODS: The cumulative incidences of postoperative complications were compared between patients who underwent total PPVs with shaving of the vitreous base (n = 22) and those who had partial PPVs or anterior vitrectomies (AVs) at the time of KPro implantation (n = 26). MAIN OUTCOME MEASURES: Rates of complications between patients who underwent total PPVs and partial PPVs or AVs. RESULTS: The rate of total postoperative complications was lower in the total PPV group (P = 0.018, log-rank test). In particular, eyes that underwent total PPVs had lower rates of retroprosthetic membranes (RPMs) requiring intervention (P = 0.049) and less vision loss due to glaucoma progression (P = 0.046). There was also a trend for fewer corneal melts (P = 0.060) and less sight-threatening complications (P = 0.051) in the total vitrectomy group. There was no difference in the rates of KPro extrusion (P = 0.41), endophthalmitis or vitritis (P = 0.15), retinal detachments (P = 0.76), cystoid macular edema (P = 0.83), or timing of complications between the 2 groups. The mean preoperative and postoperative visual acuities were similar between the 2 groups (P = 0.97). The mean follow-up was 49±22 months. CONCLUSIONS: Eyes that underwent total PPVs during implantation of aphakic, snap-on, type I Boston KPros had less postoperative complications than eyes with partial PPVs or AVs during the average 4 years of follow-up.

EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF MULTIPLE EVANESCENT WHITE DOT SYNDROME: New Insights Into Pathogenesis.

PURPOSE: To localize the various levels of abnormalities in multiple evanescent white dot syndrome by comparing "en face" optical coherence tomography (OCT) and OCT angiography with various conventional imaging modalities. METHODS: In this retrospective case series, multimodal imaging was performed in 9 retinal centers on 36 patients with multiple evanescent white dot syndrome and included widefield fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography, and B-scan and "en face" C-scan enhanced depth imaging and spectral domain OCT. Optical coherence tomography angiography was also performed at the level of the superficial and deep retinal capillary plexus and choroid. RESULTS: Multiple evanescent white dot syndrome lesions were more numerous and more easily detectable with FA and FAF. Two types of lesions were identified with FAF, FA, and indocyanine green angiography: larger widely scattered "spots" (approximately 200 µ in diameter) that were hyperfluorescent with FA, hyperautofluorescent with FAF, and hyporeflective in indocyanine green angiography, representing abnormalities primarily at the retinal pigment epithelium/photoreceptor junction; and punctate "dots" (less than 100 µ in diameter) that were hyperfluorescent with FA, hyperautofluorescent, or isoautofluorescent with FAF, and hypofluorescent with indocyanine green angiography and that localized to the outer nuclear layer. These lesions colocalized with "en face" OCT. The larger confluent "spots" were hyporeflective and colocalized to the level of the ellipsoid zone, whereas smaller hyperreflective "dots" colocalized to the outer nuclear layer. The location of the "dots" in the outer nuclear layer was further confirmed by structural spectral domain optical coherence tomography which showed coalescence of the dots into hyperreflective lines extending from the external limiting membrane to the outer plexiform layer in certain cases. Optical coherence tomography angiography analysis of the retinal microvasculature and choriocapillaris and choroid were entirely unremarkable in 100% of our patients. CONCLUSION: By combining multimodal imaging, the authors propose that multiple evanescent white dot syndrome is primarily the result of inflammation at the outer photoreceptor level leading to a "photoreceptoritis" and causing loss of the inner and outer segments. Its evanescent nature suggests that the photoreceptor cell bodies remain intact ensuring complete recovery of the photoreceptor inner and outer segments in most cases, compatible with the clinical course of spontaneous resolution of white spots and dots.

EXPANDED CLINICAL SPECTRUM OF MULTIPLE EVANESCENT WHITE DOT SYNDROME WITH MULTIMODAL IMAGING.

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

Postoperative Hemorrhagic Occlusive Retinal Vasculitis: Expanding the Clinical Spectrum and Possible Association with Vancomycin.

PURPOSE: To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN: Retrospective case series. SUBJECTS: Eleven eyes of 6 patients from 6 different institutions. METHODS: Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES: Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS: Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS: Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.

Peripapillary serous detachment in multiple evanescent white dot syndrome.

BACKGROUND: To report the presence of transient peripapillary serous detachments in multiple evanescent white dot syndrome. METHODS: Retrospective case series. RESULTS: Four eyes of four patients diagnosed with multiple evanescent white dot syndrome presented with peripapillary serous detachments. Diagnosis was based on clinical presentation, fundus findings, and angiographic findings. All 4 were female with age ranges between 24 and 40 years and presented with photopsias, an enlarged scotoma contiguous with the blind spot, and chorioretinal white dots in the posterior pole with characteristic angiographic features. All of the serous detachments resolved or were greatly reduced concomitantly with the resolution of the patient's other clinical symptoms and fundus findings. CONCLUSION: The authors report peripapillary serous detachments as a previously unreported manifestation of multiple evanescent white dot syndrome. These seem to be self limited with concurrent resolution with the rest of the patient's symptoms.

Optical coherence tomography-guided ranibizumab injection for cystoid macular edema in well-controlled uveitis: twelve-month outcomes.

PURPOSE: To determine whether serial ranibizumab injections are effective in the treatment of cystoid macular edema in patients with chronic controlled noninfectious uveitis. METHODS: Five eyes of 5 patients were included in a prospective noncomparative therapeutic trial. They received intravitreal injections of ranibizumab at Day 0 and were followed monthly for 1 year. Injections were repeated monthly if persistent or new cystic edema manifested on optical coherence tomography. The primary outcome measure was the mean change in best-corrected visual acuity from baseline at 12 months. Secondary outcome measures included mean percentage change in central subfield retinal thickness (CST) and incidence of adverse events through Month 24. RESULTS: Thirty-two injections were performed over the study period. At 1 year, the mean increase in acuity was 12.2 Early Treatment for Diabetic Retinopathy Study letters (P = 0.015). There was a statistically significant increase in visual acuity over time (P = 0.002). The CST decreased by 31.4%, 46.0%, 37.6%, and 45.4% relative to baseline at 3, 6, 9, and 12 months, respectively (P = 0.003). One patient experienced recurrence of uveitis with subsequent cataract and glaucoma progression. CONCLUSION: Optical coherence tomography-guided monthly intravitreal ranibizumab injections delivered over the course of 1 year resulted in improved vision and reduced central retinal thickness.

Spectral domain optical coherence tomography findings in patients with acute syphilitic posterior placoid chorioretinopathy.

PURPOSE: To describe the appearance of acute syphilitic posterior placoid chorioretinitis, a rare ocular manifestation of syphilis, on spectral domain optical coherence tomography (SD OCT) both before and after treatment. METHODS: Ophthalmic examination and imaging studies of 30 eyes of 19 confirmed cases were analyzed both at the time of presentation and at each follow-up visit. Patients with SD OCT and fluorescein angiography at the time of presentation, and at least three documented follow-up visits after initiation of therapy, were included in the study. Standard treatment of neurosyphilis was given to each patient, including 4 million units of penicillin G administered intravenously every 4 hours for 14 days. RESULTS: Fundus examination and imaging studies were consistent with previous reports and confirmed the diagnosis of acute syphilitic posterior placoid chorioretinitis. In 13 eyes (43.3%), baseline SD OCT scans were performed within 1 to 2 days of presentation and revealed a small amount of subretinal fluid, disruption of the inner segment/outer segment junction, and hyperreflective thickening of the retinal pigment epithelium (RPE). All 30 eyes were again scanned between Days 7 and 9 after presentation and revealed loss of the inner segment/outer segment and OS/RPE bands, and irregular hyperreflectivity of the RPE with prominent nodular elevations but without subretinal fluid. Early disruption of the external limiting membrane and punctate choroidal hyperreflectivity were seen in 1 of the 30 eyes (3.3%) and 14 of the 30 eyes (46.6%), respectively. Vision improved and the outer retinal abnormalities normalized in 28 of the 30 eyes (93.3%) after the treatment of neurosyphilis. The external limiting membrane, inner segment/outer segment band, and/or linear outer segment/RPE junction remained substantially abnormal despite treatment in 2 eyes left with 20/200 vision. CONCLUSION: Patients with acute syphilitic posterior placoid chorioretinitis show characteristic outer retinal abnormalities on SD OCT imaging, including disruption of the inner segment/outer segment band, nodular thickening of the RPE with loss of the linear outer segment/RPE junction, and, in some cases, loss of the external limiting membrane, accumulation of subretinal fluid, and punctate hyperreflectivity in the choroid. Vision improved and these abnormalities reversed after treatment of neurosyphilis in most of the patients. Persistently, poor vision despite treatment was associated with long-term loss or disruption of outer retinal anatomy on SD OCT.

Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration.

There is no treatment available for vision loss associated with advanced dry age-related macular degeneration (AMD) or geographic atrophy (GA). In a pilot, proof of concept phase 2 study, we evaluated ciliary neurotrophic factor (CNTF) delivered via an intraocular encapsulated cell technology implant for the treatment of GA. We designed a multicenter, 1-y, double-masked, sham-controlled dose-ranging study. Patients with GA were randomly assigned to receive a high-or low-dose implant or sham surgery. The primary endpoint was the change in best corrected visual acuity (BCVA) at 12 mo. CNTF treatment resulted in a dose-dependent increase in retinal thickness. This change was followed by visual acuity stabilization (loss of less than 15 letters) in the high-dose group (96.3%) compared with low-dose (83.3%) and sham (75%) group. A subgroup analysis of those with baseline BCVA at 20/63 or better revealed that 100% of patients in the high-dose group lost <15 letters compared with 55.6% in the combined low-dose/sham group (P = 0.033). There was a 0.8 mean letter gain in the high-dose group compared with a 9.7 mean letter loss in the combined low-dose/sham group (P = 0.0315). Both the implant and the implant procedure were well-tolerated. These findings suggest that CNTF delivered by the encapsulated cell technology implant appears to slow the progression of vision loss in GA, especially in eyes with 20/63 or better vision at baseline.

Internal drainage for chronic macula-involving serous retinal detachment in idiopathic central serous chorioretinopathy.

Conventional treatment of idiopathic central serous chorioretinopathy (ICSC) consists of argon laser, photodynamic therapy, or observation. However, in cases of atypical bullous ICSC with exudative detachment preventing any laser therapy, a surgical approach with external drainage of fluid has been performed. We present a case of ICSC with persistent macula involving exudative retinal detachment without evidence of uveitis that responded favorably to internal drainage by vitrectomy along with a scleral buckle placement. Our case, treated with internal drainage, also demonstrated successful long-term reattachment of the serous retinal detachment without any additional complications from the surgery.

Update on "Cell Therapy" Clinics Offering Treatments of Ocular Conditions Using Direct-To-Consumer Marketing Websites in the U.S.

PURPOSE: To assess the scope of U.S.-based companies advertising and administering non-Federal Drug Administration (FDA) approved cell-based therapy (herein called NFACT) for ocular conditions based on information from companies' public websites after the FDA's legal actions against specific NFACT clinics in 2018 and 2019. Current findings are compared to previously published data from 2017. DESIGN: Trend study looking at U.S.-based companies that use direct-to-consumer marketing and have websites advertising therapy for ocular conditions. METHODS: A systematic and extensive keyword-based Internet search was utilized to identify, document, and analyze U.S. business websites offering NFACT for ocular conditions as of August 2022. Main outcomes measured include, clinic locations, marketed ocular conditions, types of NFACT offered, source of stem cells used, routes of administration, and treatment costs. RESULTS: From the prior analysis in 2017 to the 2019 analysis, there was a decrease in the number of NFACT clinics from 76 to 62 and companies from 40 to 39. Given the concerning persistence of NFACTs in August 2019 an additional analysis was performed in 2022 which showed a drastic decrease in NFACT clinics from 62 in 2019 to 18 in 2023 and from 39 companies to 13 in 2023. In both 2019 and 2022, the most commonly referenced ocular condition was age-related macular degeneration (2019 - 72%, 2022 - 92%). The state with the most clinics was in Texas (2019 - 12; 2022 - 5). Autologous adipose-derived stem cells were the most common cell type used in both analyses. CONCLUSIONS: In 2019 U.S.-based direct-to-consumer companies marketing NFACT persisted despite (1) a lack of high-quality clinical evidence supporting the efficacy of these procedures, (2) the association of some of these treatments with severe vision loss, and (3) increasing FDA oversight and recent legal action. In 2022 the number of clinics and companies decreased, but their persistence is a reminder that continued concern is necessary and ophthalmic associations need to continue advocacy efforts to protect patients from these potentially predatory organizations.

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma: Safety, Neuroprotection, and Neuroenhancement.

Purpose: To assess the safety and efficacy of a ciliary neurotrophic factor (CNTF) intraocular implant on neuroprotection and neuroenhancement in glaucoma. Design: Open-label, prospective, phase I clinical trial. Participants: A total of 11 participants were diagnosed with primary open-angle glaucoma (POAG). One eye of each patient was assigned as the study (implant) eye. Methods: The study eye was implanted with a high-dose CNTF-secreting NT-501 implant, whereas the other eye served as a control. All patients were followed up for 18 months. Analysis was limited to descriptive statistics. Main Outcome Measures: Primary outcome was safety through 18 months after implantation assessed by serial eye examinations, structural and functional testing, and adverse events (AEs) recording. Parameters measured included visual acuity (VA), Humphrey visual field (HVF), pattern electroretinogram, scanning laser polarimetry with variable corneal compensation (GDx VCC), and OCT. These parameters were also used for secondary analysis of efficacy outcome. Results: All NT-501 implants were well tolerated with no serious AEs associated with the implant. The majority of AEs were related to the implant placement procedure and were resolved by 12 weeks after surgery. Foreign-body sensation was the most commonly reported AE and was self-limited to the postoperative period. The most common implant-related AE was pupil miosis; no patients underwent explant. Visual acuity and contrast sensitivity decreased more in fellow eyes than in study eyes (VA, -5.82 vs. -0.82 letters; and contrast sensitivity, -1.82 vs. -0.37 letters, for fellow vs. study eyes, respectively). The median HVF visual field index and mean deviation measurements worsened (decreased) in fellow eyes (-13.0%, -3.9 dB) and improved (increased) in study eyes (2.7%, 1.2 dB). Implanted eyes showed an increase in retinal nerve fiber layer thickness measured by OCT and by GDx VCC (OCT, 2.66 µm vs. 10.16 µm; and GDx VCC, 1.58 µm vs. 8.36 µm in fellow vs. study eyes, respectively). Conclusions: The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements suggesting biological activity, supporting the premise for a randomized phase II clinical trial of single and dual NT-501 CNTF implants in patients with POAG, which is now underway. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.