Phylogenetic and Recombination Analysis of Clinical Vitreous Humor-Derived Adenovirus Isolates Reveals Discordance Between Serotype and Phylogeny.

Purpose: To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye Institute. Methods: The PacBio Sequel II was used to sequence the genomes of the three clinical adenovirus isolates. To identify the isolates, a full genome-based multiple sequence alignment (MSA) of 722 mastadenoviruses was generated using multiple alignment using fast Fourier transform (MAFFT). MAFFT was also used to generate genome-based human adenovirus B (HAdV-B) MSAs, as well as HAdV-B fiber, hexon, and penton protein-based MSAs. To examine recombination within HAdV-B, RF-Net 2 and Bootscan software programs were used. Results: In the course of classifying three new atypical ocular adenovirus samples, taken from the vitreous humor, we found that all three isolates were HAdV-B species. The three Bascom Palmer HAdV-B genomes were then combined with over 300 HAdV-B genome sequences, including nine ocular HAdV-B genome sequences. Attempts to categorize the penton, hexon, and fiber serotypes using phylogeny of the three Bascom Palmer samples were inconclusive due to incongruence between serotype and phylogeny in the dataset. Recombination analysis using a subset of HAdV-B strains to generate a hybridization network detected recombination between nonhuman primate and human-derived strains, recombination between one HAdV-B strain and the HAdV-E outgroup, and limited recombination between the B1 and B2 clades. Conclusions: The discordance between serotype and phylogeny detected in this study suggests that the current classification system does not accurately describe the natural history and phylogenetic relationships among adenoviruses.

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.

Perifoveal exudative vascular anomalous complex and resembling lesions treated with intravitreal triamcinolone.

PURPOSE: To report the use of intravitreal triamcinolone to treat macular edema associated with isolated perifoveal exudative vascular anomalous complex (PVAC) and resembling lesion (PVAC-RL). METHODS: In this case series, three diabetic patients (3 eyes) with PVAC-RLs and one healthy patient (1 eye) with PVAC lesion associated with cystic spaces underwent three intravitreal injections of aflibercept before switching to one intravitreal triamcinolone injection in each patient. RESULTS: Macular edema improved from 297.5 ± 8.10 µm, at baseline, to 269.2 ± 8.89 µm, after triamcinolone; whereas visual acuity improved from 20/38 to 20/26 (ETDRS). CONCLUSION: PVAC and PVAC-RL are rare and often misdiagnosed lesions that may be associated with decreased vision. Our outcomes suggest that intravitreal injection of triamcinolone may be an effective and affordable treatment for PVAC and PVAC-RL with intraretinal fluid.

A Cost-Effectiveness Analysis of Pegcetacoplan for the Treatment of Geographic Atrophy.

PURPOSE: To evaluate the cost-effectiveness of the treatment of geography atrophy (GA) with intravitreal pegcetacoplan and to identify utility-measurement surrogates. DESIGN: Cost analysis based on data from a published study. SUBJECTS: None; based on data from published sham control compared with 2 treatment groups in the index study. METHODS: Costs were based on 2022 Medicare reimbursement data. Specific outcomes were extrapolated from the DERBY and OAKS trials. Assumptions were made for the lifetime analysis based on a theoretical logistic growth model of the atrophy. OUTCOME MEASURES: Cost, cost utility, cost per quality-adjusted life-year, and cost per area of GA (in US$). RESULTS: The costs to treat GA in every month (EM) and every-other-month (EOM) treatment groups over the 2 years as reported were $70 000 and $34 600, respectively. The costs per area of delaying GA for 2 years in all patients were $87 300/mm2 (EM) and $49 200/mm2 (EOM), and in initially extrafoveal patients, $53 900/mm2 (EM) and $32 100/mm2 (EOM). The costs per day of delaying GA for 2 years were $295 (EM) and $170 (EOM); the marginal cost (EM vs. EOM) per retinal pigment epithelium cell saved was $30. The modeled lifetime costs were $350 000 (EM) and $172 000 (EOM), or $309 000/mm2 (EM) and $180 000 (EOM) /mm2. The modeled time to 95% atrophy at 13 years was delayed by 2.5 years (EM) and 2.1 years (EOM). The costs/quality-adjusted life-year gained based on modeled visual loss with 95% atrophy were $706 000 (EM) and $397 000 (EOM). CONCLUSION: Treatment of GA with intravitreal pegcetacoplan EOM was more cost effective than EM. Treatment of extrafoveal lesions yielded greater utility than the treatment of the entire group. As atrophy progression approaches an upper limit, the marginal cost/benefit ratios increase. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

RETINAL VASCULAR DISEASE IN LIMB-GIRDLE MUSCULAR DYSTROPHY.

PURPOSE: To report bilateral retinal vascular occlusive disease in limb-girdle muscular dystrophy (LGMD). METHODS: Case report. RESULTS: A 34-year-old Asian woman was referred for evaluation and management of central retinal vein occlusion. Ultra-wide-field fluorescein angiography showed resolving initial peripheral retinal vein occlusion in one eye and peripheral venular segmental staining in the fellow asymmetric eye. Genetic testing established the diagnosis of LGMD. CONCLUSION: Similar to other forms of muscular dystrophy, LGMD is caused by genetic abnormalities in sarcolemma proteins, a key structural component that connects the intracellular cytoskeleton of a myofiber to the extracellular matrix. Like other muscular dystrophies, LGMD may be associated with retinal vascular abnormalities noted. In this case, retinal vascular smooth muscle dysfunction was seen in LGMD, analogous to reported vascular abnormalities in other muscular dystrophies such as facioscapulohumeral dystrophy and Duchenne muscular dystrophy.

Clinical Outcome of Cystoid Macular Edema in Silicone Oil-Filled Eyes.

Purpose: To investigate the clinical outcome of cystoid macular edema (CME) in eyes undergoing silicone oil (SO) tamponade with subsequent SO removal (SOR). Methods: A retrospective case series of adult patients with CME treated with SO tamponade and SOR was conducted between January 2015 and January 2021. Exclusion criteria included eyes with a prior SO tamponade, those that did not undergo SOR, or those with infectious/inflammatory diagnoses. The primary outcomes were the incidence and resolution rates of CME in eyes with SO tamponade that had undergone SOR. The secondary outcomes included changes in best-corrected visual acuity (BCVA) and central field thickness (CFT). Results: Nineteen eyes of 19 patients (58% men) aged 52 years (interquartile range [IQR], 45-66 years) met the study inclusion criteria. The median (IQR) follow-up duration post SOR was 22 (8-35) months. The mean CFT decline for the CME-resolved cases was 13.1 µm/mo (P = .257). CME resolved in only 10 eyes (53%), 7 (67%) of which occurred after SOR. The median (IQR) BCVA was 20/400 (20/200 to 20/1262) at CME diagnosis and 20/796 (20/252 to hand motions) after SOR, with 0.184 worsening in logMAR BCVA (P = .340). Medical treatment was not associated with CME resolution compared with observation (50% vs 89%, respectively; P = .069). Eyes with proliferative vitreoretinopathy (PVR) had a higher rate of persistent CME compared with eyes with other diagnoses (78% vs 10%, respectively; P = .005). Conclusions: Nearly half had nonresolution of CME after SO was removed. The VA at the last follow-up was unaffected by CME resolution. Preoperative PVR may be a risk factor for unresolved CME.

Endophthalmitis caused by Burkholderia cepacia complex (BCC): clinical characteristics, antibiotic susceptibilities, and treatment outcomes.

PURPOSE: To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis. STUDY DESIGN: Retrospective, observational case series. METHODS: Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed wisth culture-confirmed endophthalmitis due to BCC. Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system. RESULTS: Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated in vitro susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1 mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%). CONCLUSIONS: Endophthalmitis caused by B. cepacia is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics.

Unexplained Vision Loss Associated With Intraocular Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment Repair.

Purpose: To evaluate the visual outcomes with unexplained vision loss during or after silicone oil (SO) tamponade. Methods: This multicenter retrospective case series comprised patients with unexplained vision loss associated with SO tamponade or its removal. Eyes with other clear secondary identifiable causes of vision loss were excluded. Results: Twenty-nine eyes of 28 patients (64% male) were identified. The mean age was 50 ± 13 years (range, 13-78 years). The mean duration of SO tamponade was 148 ± 38 days. Eighteen eyes (62%) developed unexplained vision loss while under SO; 11 (38%) had vision loss after SO removal. The most common optical coherence tomography (OCT) finding was ganglion cell layer (GCL) thinning (55%). Eyes with vision loss after SO removal had a mean logMAR best-corrected visual acuity (BCVA) of 0.6 ± 0.7 (Snellen 20/85) before SO tamponade and 1.2 ± 0.4 (20/340) before SO removal. By the last follow-up after SO removal, the BCVA had improved to 1.1 ± 0.4 (20/235). In eyes with vision loss after SO removal, the BCVA before SO removal was 0.7 ± 0.7 (20/104), which deteriorated to 1.4 ± 0.4 (20/458) 1 month after SO removal. By the last follow-up, the BCVA had improved to 1.0 ± 0.5 (20/219). Conclusions: Unexplained vision loss can occur during SO tamponade or after SO removal. Vision loss was associated with 1000-centistoke and 5000-centistoke oil and occurred in macula-off and macula-on retinal detachments. The duration of tamponade was 3 months or longer in the majority of eyes. Most eyes had GCL thinning on OCT. Gradual visual recovery can occur yet is often incomplete.

Familial Exudative Vitreoretinopathy-Like Phenotype in a Patient With Microcephaly and TUBGCP6 Mutations.

Purpose: To describe a case of microcephaly, unilateral retinal fold, and familial exudative vitreoretinopathy (FEVR)-like phenotype in the context of 2 TUBGCP6 variants. Methods: A case and its findings were analyzed. Results: A 4-month-old boy with no family history of eye disease presented by referral for management of presumed persistent fetal vasculature in the left eye. An external examination showed microcephaly. The patient grimaced to light in both eyes, and the anterior segments were unremarkable. On dilated fundus examination, diffuse chorioretinal atrophy was present bilaterally. In the left eye, a retinal fold emanated from the optic nerve head. There was early termination of retinal vasculature, especially in zone 3 in the left eye, resembling a FEVR-like phenotype. Panel-based genetic testing was performed and found 2 mutations in TUBGCP6. Conclusions: Microcephaly, chorioretinopathy, and retinal folds may be associated with TUBGCP6 mutations and masquerade as PFV.

Trends in Immunosuppressive Agent Use for Non-Infectious Uveitis by US Ophthalmologists in Medicare Beneficiaries and Association with Physician-Industry Interactions.

PURPOSE: To report the trends of immunosuppressive drug use for non-infectious uveitis and explore their relationship with industry payments. METHODS: A retrospective review of ophthalmologists reimbursed by Medicare for the administration of adalimumab (ADA), repository corticotropin (RCI), methotrexate (MTX), and mycophenolate mofetil (MMF) between 2014 and 2018. RESULTS: A total of 316 ophthalmologists were reimbursed by Medicare for 1567 ADA, 465 RCI, 1752 MTX, and 12 333 MMF administrations. The number and dollar amount of industry payments were positively associated with ADA and RCI use (P < 0.001). From 2014 to 2018, there was a positive trend in the proportion of ADA (P = 0.007) and RCI (P = 0.007) used and negative trend in the proportion of MMF (P = 0.025) used. CONCLUSION: From 2014 to 2018, the use of ADA and RCI increased while MMF decreased and MTX remained stable. There was a positive association between ADA and RCI use and physician-industry interactions. A causal relationship is not determined.

Retinal Detachments in Pediatric Patients With X-Linked Retinoschisis: Characteristics and Surgical Outcomes.

BACKGROUND AND OBJECTIVE: Retinal detachments (RDs) are a complication of X-linked retinoschisis (XLRS) with a poor prognosis. This study aims to report outcomes of XLRS-RD repair in pediatric patients. MATERIALS AND METHODS: The study is a retrospective analysis of pediatric patients undergoing vitreoretinal surgery for XLRS-RDs from 2000 to 2022. RESULTS: Nine patients (11 eyes) met inclusion criteria. All patients were boys, with a mean age of 8 years. Most RDs arose inferiorly (64%). Seven (64%) detachments were macula-involving. Seven (64%) detachments were repaired with combined scleral buckling and vitrectomy, two (18%) detachments were repaired with vitrectomy alone, one (9%) detachment underwent a primary scleral buckling procedure, and one (9%) asymptomatic detachment with a pigment demarcation line was observed. Silicone oil was used in eight of nine (89%) eyes undergoing vitrectomy. Final visual acuity was 20/200 or better in eight (73%) eyes. One eye that underwent surgical intervention remained unattached at follow-up. CONCLUSION: Surgical repair in patients with XLRSRDs was associated with successful reattachment, although visual prognosis varied. [Ophthalmic Surg Lasers Imaging Retina 2023;54:574-579.].

NATIONWIDE DEMOGRAPHIC DISPARITIES IN UNITED STATES EMERGENCY DEPARTMENT VISITS IN PATIENTS WITH RHEGMATOGENOUS RETINAL DETACHMENT.

BACKGROUND/PURPOSE: Within the evolving landscape of healthcare in the United States (US), delineating the demographic nuances and financial implications of emergent conditions, such as rhegmatogenous retinal detachment (RRD), is paramount. This study seeks to analyze the demographic and hospital billing amount/cost of service disparities in RRD visits to emergency departments (EDs) nationwide. METHODS: We conducted a retrospective, cross-sectional, population-based study using International Classification of Diseases, 10th revision , and Current Procedural Terminology codes in the 2016 to 2019 Nationwide Emergency Department Sample databases to identify RRD visits. The analysis included demographics, hospital billing amount, and cost of service of RRD ED management. RESULTS: A total of 12,492 RRD encounters were identified with men constituting 64% and a prominent age group being 50 to 64 years (49.3%). Most patients (90%) were managed in metropolitan teaching hospitals, predominantly in the southern U.S. region (56.1%). Private insurance covered 45% of patients. Same-day RRD repair odds increased in November and December. Whites had a higher likelihood for same-day treatment. Hospital billing amount rose from $23,600 in 2016 to $30,354 in 2019, with stable mean total cost of service. Rhegmatogenous retinal detachment ED visit incidence did not show seasonal variation ( P = 0.819). CONCLUSION: Most patients with RRD in U.S, EDs were middle-aged men, with Whites more likely to receive same-day repair. There was no sex bias observed in same-day repair decision-making. Although hospital billing amount increased over the study period, total cost of service remained stable. The incidence of RRD ED visits showed no seasonal variation.

Retinal displacement following repair of rhegmatogenous retinal detachment.

Retinal displacement following the repair of rhegmatogenous retinal detachment (RRD) has been reported in recent studies. It was described as vertical movement of the retinal relative to its original location, as evidenced by retinal vessel printing on fundus autofluorescence imaging. This review reports the current literature on retinal displacement. We conducted an English literature search using Medline, PubMed, Embase, and Web of Science. We have reviewed 22 articles describing the diagnosis, frequency, and possible risk factors for retinal displacement. The reported rate of retinal displacement ranged from 6.4% to 62.8%, and the possible risk factors included the detachment-to-repair time, location and extent of RRD, macula-off RD, presence of subretinal fluid, use of perfluorocarbon, use of tamponade, postoperative facedown positioning, type of RRD repair, and presence of proliferative vitreoretinopathy, especially high grade. This review increases awareness of retinal displacement and its associated visual effects.

Endophthalmitis caused by Burkholderia cepacia complex (BCC): Clinical characteristics, antibiotic susceptibilities, and treatment outcomes.

Purpose: To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis. Study design: Retrospective, observational case series. Methods: Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed with culture-confirmed endophthalmitis due to BCC. Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system. Results: Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated in vitro susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%). Conclusions: Endophthalmitis caused by B. cepacia is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics.

Phylogenetic and Genomic Characterization of Whole Genome Sequences of Ocular Herpes Simplex Virus Type 1 Isolates Identifies Possible Virulence Determinants in Humans.

Purpose: There are limited data on the prevalence and genetic diversity of herpes simplex virus type 1 (HSV-1) virulence genes in ocular isolates. Here, we sequenced 36 HSV-1 ocular isolates, collected by the Bascom Palmer Eye Institute, a university-based eye hospital, from three different ocular anatomical sites (conjunctiva, cornea, and eyelid) and carried out a genomic and phylogenetic analyses. Methods: The PacBio Sequel II long read platform was used for genome sequencing. Phylogenetic analysis and genomic analysis were performed to help better understand genetic variability among common virulence genes in ocular herpetic disease. Results: A phylogenetic network generated using the genome sequences of the 36 Bascom Palmer ocular isolates, plus 174 additional strains showed that ocular isolates do not group together phylogenetically. Analysis of the thymidine kinase and DNA polymerase protein sequences from the Bascom Palmer isolates showed multiple novel single nucleotide polymorphisms, but only one, BP-K14 encoded a known thymidine kinase acyclovir resistance mutation. An analysis of the multiple sequence alignment comprising the 51 total ocular isolates versus 159 nonocular strains detected several possible single nucleotide polymorphisms in HSV-1 genes that were found significantly more often in the ocular isolates. These genes included UL6, gM, VP19c, VHS, gC, VP11/12, and gG. Conclusions: There does not seem to be a specific genetic feature of viruses causing ocular infection. The identification of novel and common recurrent polymorphisms may help to understand the drivers of herpetic pathogenicity and specific factors that may influence the virulence of ocular disease.