Review and analysis of history and utilization of panretinal photocoagulation and ranibizumab after publication of protocol S.

PURPOSE OF REVIEW: We describe the history, utilization, and series results of panretinal photocoagulation (PRP) and ranibizumab and provide an analysis of PRP and ranibizumab usage before versus after the publication of the 2-year and 5-year results of the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S trial. RECENT FINDINGS: Number of ranibizumabs performed began to increase and number of PRPs performed began to decrease in 2016. After publication of the 2-year results, there was significant negative trend in PRP services and significant positive trend in ranibizumab services (both P < 0.001). After publication of the 5-year results, there was significant negative trend in PRP services (P = 0.003). There were significant negative trends (all P < 0.001) in reimbursement factors for PRP from 2013 to 2020: average work RVU (wRVU), nonfacility physical expense RVU, facility PE RVU, malpractice RVU (MP RVU). SUMMARY: Both PRP and ranibizumab have undergone numerous trials comparing their efficacy to other treatment options or no treatment at all. The publication of the 2-year results of Protocol S was associated with an increase in utilization of ranibizumab and decrease in utilization of PRP, with continued decrease after the publication of the 5-year results.

Efficacy and Safety of Anti-VEGF Injections and Surgery for AMD-Related Submacular Hemorrhage: A Systematic Review & Meta-Analysis.

TOPIC: This systematic review and meta-analysis investigates the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) injections compared to surgical intervention in improving visual acuity (VA) and reducing complications for patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (AMD). CLINICAL RELEVANCE: Determining the optimal intervention for SMH in AMD is crucial for patient care. METHODS: We included studies on anti-VEGF injections or surgical interventions for SMH in AMD from 7 databases, searched up to May 2024. Data extraction and quality assessment were done by two independent reviewers. Certainty of evidence was assessed GRADE approach. Meta-analysis employed random-effects models. Primary outcomes were pooled mean logMAR VA difference (initial examination minus last follow-up VA) and adverse events rates. RESULTS: A total of 43 observational studies were included: 21 (960 eyes) on anti-VEGF and 22 (455 eyes) on surgery. Comparisons were made across separate studies due to lack of head-to-head studies. Meta-analysis included 11 anti-VEGF studies (444 eyes) and 12 surgical studies (195 eyes) for VA outcomes. The mean difference (MD) in VA was -0.16 (95%CI: -0.26,-0.07) for anti-VEGF and -0.36 (95%CI: -0.68,-0.04) for surgery, with no significant difference between groups (X2=1.70, df =1, p=0.19). Heterogeneity was high in surgical studies (I2=96.2%, tau2=0.23, p<0.01) and negligible in anti-VEGF studies (I2=7%, tau2=0.003, p=0.38). GRADE certainty was moderate for anti-VEGF and low for surgery. Anti-VEGF had lower rates of cataract (0% vs 4.6%), proliferative vitreoretinopathy (PVR, 0.1% vs 2.0%), and retinal detachment (RD, 0.1% vs 10.6%), but similar rates of recurrent hemorrhage (5.4% vs 5.3%). Complications were summarized descriptively due to zero cell problem. CONCLUSION: Both anti-VEGF and surgery treat SMH in AMD with similar VA outcomes but different safety profiles. Anti-VEGF is preferred for less severe hemorrhage, while surgery is suited for extensive hemorrhage. Despite uncertain comparative VA outcomes, treatment should be guided by clinical judgment and patient factors.

Potential Risk Factors for Ocular Pain in Patients Undergoing Multiple Intravitreal Injections of Anti-Vascular Endothelial Growth Factor.

Purpose: To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. Methodology: This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. Results: In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Conclusion: Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.

Faricimab in Previously Treated Eyes With Neovascular Age-Related Macular Degeneration: An Assessment of Durability and Treatment Outcomes.

BACKGROUND AND OBJECTIVE: This study evaluated the efficacy and durability of faricimab in patients with neovascular age-related macular degeneration (nAMD) who were previously treated with anti-vascular endothelial growth factor (anti-VEGF) agents. PATIENTS AND METHODS: This retrospective case series was conducted at a single tertiary center in the United States. It focused on nAMD patients who transitioned to faricimab after initial anti-VEGF therapy, with a follow-up period of at least 9 months. "Complete dryness" was defined as the absence of intra- and/or subretinal fluid on optical coherence tomography. Durability was gauged by the extension of treatment intervals relative to the injection frequency of the previous agent. RESULTS: Sixty-two eyes from 62 patients were included. Treatment interval ranged from 5 to 10 weeks; 10 (16%) patients were able to be extended by 2 or more weeks compared to their previous regimen. Median (interquartile range [IQR]) central field thickness was 310 µm (254, 376) on initiating faricimab and declined by the ninth month (P values at 3, 6, and 9 months were 0.01, 0.02, and 0.07, respectively). Median (IQR) visual acuity at initiation of faricimab was 0.4 (0.20, 0.50) and did not change by the ninth month. Complete anatomical dryness was present in 10 (16%) eyes before switching; 90% remained dry at 9 months. Of 52 (84%) incompletely dry eyes before switching, 15% achieved complete dryness by 9 months on faricimab. CONCLUSIONS: Faricimab modestly improved the treatment intervals for a small proportion of previously treated patients on anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

A Cost Effectiveness Analysis of Avacincaptad Pegol for the Treatment of Geographic Atrophy with Comparison to Pegcetacoplan.

PURPOSE: The purpose of this study was to evaluate the cost effectiveness of the treatment of geographic atrophy (GA) with intravitreal avacincaptad pegol (ACP) and to compare it with pegcetacoplan (PEG). DESIGN: Cost analysis based on data from published studies. SUBJECTS: None; based on data from published sham control compared with 2 treatment groups in each of the index studies. METHODS: Costs were based on 2022 Medicare reimbursement data for both facility (hospital-based) and nonfacility settings in Miami. Specific usage and outcomes were derived from the GATHER2 study as well as DERBY and OAKS trials. For ACP, all patients were treated every month (EM) in year 1 then randomized to every other month (EOM) or EM in year 2. Two-year models were created for patients in the facility setting for extrafoveal (ACP and PEG) and all patients (PEG). MAIN OUTCOME MEASURES: Cost, cost utility, and cost per area of GA (in United States dollars). RESULTS: The cost to treat GA with ACP in EM and EOM treatment groups over the 2 years as reported was $67 400 and $40 600, respectively. With ACP treatment over 2 years, the daily cost of delaying GA 3.4 months (EM) and 4.5 months (EOM) was $649 (EM) and $356 (EOM). The (facility-based) costs per unit area of retinal pigment epithelium saved for patients with extrafoveal GA over the 2-year period were $119 000/mm2 (EM ACP) versus $54 000/mm2 (EM PEG) (P < 0.001), $57 100/mm2 (EOM ACP) versus $31 400/mm2 (EOM PEG) (P < 0.001), and $45 300/mm2 (hypothetical EOM from outset ACP). CONCLUSION: Treatment of GA with intravitreal ACP EOM was more cost effective than EM. When assessing extrafoveal lesions, ACP was less cost effective than PEG for both EM and EOM treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Review and analysis of history and utilization of pneumatic retinopexy after pneumatic retinopexy versus vitrectomy for the management of primary rhegmatogenous retinal detachment outcomes randomized trial (PIVOT).

PURPOSE OF REVIEW: We describe the history and series results of pneumatic retinopexy (PnR)and provide an analysis of PnR utilization after publication of results of pneumatic retinopexy versus vitrectomy for the management of primary rhegmatogenous retinal detachment outcomes randomized trial (PIVOT). RECENT FINDINGS: No significant trends were found for average number of services ( P  = 0.153) of PnR after the publication of PIVOT results. SUMMARY: PnR is a rhegmatogenous retinal detachment (RRD) repair technique that was first described in the early 1900 s and has evolved over time to become a modern-day, minimally invasive, underutilized treatment option. Other repair techniques for RRD include scleral buckling and pars plana vitrectomy (PPV), which has been compared to the use of PnR in PIVOT. Results of PIVOT concluded that PnR offered superior visual acuity and noninferiority. PnR is underutilized in the United States even after publication of results of PIVOT deemed it a noninferior treatment. Lack of a significant increase in national utilization of PnR could be associated with multifactorial clinician, systems, and financial reasons in the real-world setting.

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.

CENTRAL BOUQUET HEMORRHAGE: Clinical and Multimodal Imaging Features.

PURPOSE: To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage." METHODS: Retrospective, observational, multicenter case series of eyes with central bouquet hemorrhage. Multimodal imaging features were reviewed and analyzed. RESULTS: Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6 ± 21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia Type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with central bouquet hemorrhage displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer. Cross-sectional optical coherence tomography showed a well-delineated round hyperreflective lesion involving the central foveal Henle fiber layer/outer nuclear layer in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented Henle fiber layer were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36). CONCLUSION: "Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with Henle fiber layer hemorrhage and encountered in a spectrum of macular disease.

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.