Treatment of geographic atrophy: an update on data related to pegcetacoplan.

PURPOSE OF REVIEW: Geographic atrophy is an advanced and currently untreatable form of age-related macular degeneration (AMD), which leads to significant compromise of visual function and quality of life. Dysregulation of the complement cascade has been directly implicated in AMD pathogenesis. Pegcetacoplan is a pegylated highly selective bicyclic peptide that inhibits the cleavage of complement component 3 (C3), which represents a key step in propagation of the complement cascade. The phase 2 FILLY trial as well as the phase 3 OAKS and DERBY trials have evaluated the safety and efficacy of pegcetacoplan for the treatment of GA. RECENT FINDINGS: The FILLY, OAKS and DERBY trials have demonstrated that local inhibition of C3 cleavage with pegcetacoplan can reduce geographic atrophy lesion growth compared with sham with an effect size of approximately 11-35% depending on the specific trial and specific geographic atrophy phenotype considered. Overall pegcetacoplan has appeared to be well tolerated with the notable side effect of a dose-dependent increase in the rate of exudative AMD development in treated eyes. SUMMARY: The FILLY, OAKS and DERBY trials have demonstrated that pegcetacoplan is a potentially viable treatment for geographic atrophy. Additional data from the 2-year outcomes of DERBY and OAKS as well as data from the ongoing 3-year GALE extension study will provide additional insights into the potential therapeutic benefit of pegcetacoplan. Future studies assessing complement inhibition at earlier stages of AMD, with the goal of preventing geographic atrophy formation, are warranted.

MANAGEMENT OF LARGE FULL-THICKNESS MACULAR HOLES: Long-Term Outcomes of Internal Limiting Membrane Flaps and Internal Limiting Membrane Peels.

BACKGROUND/PURPOSE: To determine and compare the efficacy of a surgical internal limiting membrane (ILM) flap technique with the traditional ILM peel on long-term visual and anatomical outcomes for large (>400 µm) full-thickness macular holes. METHODS: From October 2016 to July 2022, patients undergoing initial full-thickness macular hole repair with the ILM flap or ILM peel technique were reviewed. Final outcomes were recorded and based on size in microns: 401 to 800, 801 to 1,200, and >1,200. RESULTS: Patients treated with ILM flap (n = 52, 94.2% closure rate) or ILM peel (n = 407, 93.6% closure rate) were followed with a mean follow-up time of 15.0 ± 10.2 and 20.0 ± 13.4 months, respectively. Success rates for ILM flaps and ILM peels were compared for full-thickness macular holes of 401 to 800 (100%, 95.8%, P = 0.39), 801 to 1,200 (95%, 93%, P = 0.74), and >1,200 (86.7%, 86.7%, P = 1.0) µm. Mean best-recorded logarithm of the minimal angle of resolution visual acuity for ILM flaps and ILM peels, respectively, was 1.02 ± 0.46 and 0.87 ± 0.47 preoperatively, with follow-up acuity of 0.48 ± 0.32 (P < 0.03) and 0.39 ± 0.42 (P < 0.01) at Year 3. CONCLUSION: Both techniques provide a similar anatomical closure rate and functional improvement in vision. Comparisons should be cautiously made based on difference in preoperative hole size.

USE OF OPTICAL COHERENCE TOMOGRAPHY IN DETECTING RETINAL TEARS IN ACUTE, SYMPTOMATIC POSTERIOR VITREOUS DETACHMENT.

PURPOSE: To evaluate the association of posterior vitreous opacities (PVOs) on optical coherence tomography with retinal tears identified on examination in patients with acute, symptomatic posterior vitreous detachment (PVD). METHODS: Data were retrospectively collected from the medical records of 388 patients with acute, symptomatic PVD between January 1, 2021, and June 30, 2021. Included patients had received a primary diagnosis of PVD and presented with flashes and/or floaters. Optical coherence tomography scans were reviewed by two separate readers for the presence of PVOs. The primary outcome was the presence of retinal tear on fundus photograph and on examination. RESULTS: Of 388 patients who presented with acute PVD symptoms, 90 (23.2%) were found to have a retinal tear on dilated fundus examination. Among these patients, 78 (86.7%) were found to have PVOs on optical coherence tomography. Statistical analysis demonstrated a significant relationship between the presence of PVOs and retinal tear ( P < 0.01). The sensitivity and specificity of this finding was 86.7% and 72.5%, respectively. Further analysis included area under the curve from receiver operating characteristic curve which was found to be 0.80. CONCLUSION: The presence of PVOs on optical coherence tomography is suggestive of a retinal tear in patients with acute, symptomatic PVD.

TOXIC POSTERIOR SEGMENT SYNDROME AFTER DROPLESS CATARACT SURGERY WITH COMPOUNDED TRIAMCINOLONE-MOXIFLOXACIN.

PURPOSE: To report toxic posterior segment syndrome after dropless cataract surgery using locally compounded triamcinolone-moxifloxacin. METHODS: A retrospective case review of 7 patients presenting with a decrease in visual acuity after dropless cataract surgery. RESULTS: All patients experienced significant reductions in best-corrected visual acuity of the postoperative eye ranging from 20/40 to count finger at 4 feet (average best-corrected visual acuity 20/220) immediately after surgery. The presenting symptoms included flashes, floaters, photophobia, glare, halos, visual distortions, and problems assessing colors. In three cases, foveal retinal pigment epithelium changes were noted on dilated fundus exam (DFE). Ellipsoid zone loss was noted on ocular coherence tomography in five of the seven affected eyes. Electrophysiology testing in five of the seven affected eyes demonstrated large decreases in full-field electroretinogram amplitude, oscillatory potentials, multifocal electroretinogram, and visual evoked potential, along with a negative electroretinogram. One patient was treated with a dexamethasone implant, but no improvement in visual acuity was noted. CONCLUSION: This is the first case series of toxic posterior segment syndrome occurring secondary to intracameral compounded triamcinolone-moxifloxacin in dropless cataract surgery. The FDA has attributed the toxicity to abnormally high levels of the binding agent poloxamer 407 in the compounded medication. Clinicians should be aware of this phenomenon and exhibit caution when using compounded medications.

Micelle-in-Liposomes for Sustained Delivery of Anticancer Agents That Promote Potent TRAIL-Induced Cancer Cell Apoptosis.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces cancer cell-specific apoptosis and has garnered intense interest as a promising agent for cancer treatment. However, the development of TRAIL has been hampered in part because most human cancer cells are resistant to TRAIL. A few small molecules including natural compounds such as piperlongumine (PL) have been reported to sensitize cancer cells to TRAIL. We prepared a novel type of nanomaterial, micelle-in-liposomes (MILs) for solubilization and delivery of PL. PL-loaded MILs were used to sensitize cancer cells to TRAIL. As visualized by cryo-TEM, micelles were successfully loaded inside the aqueous core of liposomes. The MILs increased the water solubility of PL by ~20 fold. A sustained PL release from MILs in physiologically relevant buffer over 7 days was achieved, indicating that the liposomes prevented premature drug release from the micelles in the MILs. Also demonstrated is a potent synergistic apoptotic effect in cancer cells by PL MILs in conjunction with liposomal TRAIL. MILs provide a new formulation and delivery vehicle for hydrophobic anticancer agents, which can be used alone or in combination with TRAIL to promote cancer cell death.

Impact of Prefilled Syringes and Masking on Postintravitreal Injection Endophthalmitis.

Purpose: To compare rates of endophthalmitis (1) following intravitreal injection of antivascular endothelial growth factor therapies with glass-vial preparation (GVP) vs prefilled syringes (PFS) and (2) before and after masking protocols were implemented. Methods: Medical records within a multicenter retina practice in Houston, Texas, from January 2015 to August 2021 were retrospectively reviewed. The primary outcome was rate of endophthalmitis after intravitreal injection. Results: A total of 307 349 injections were performed during the study period and 101 cases of endophthalmitis were identified (0.033%). PFS use was associated with a decreased risk of endophthalmitis (relative risk [RR], 0.320; 95% CI, 0.198-0.518, P < .001); 54 cases of endophthalmitis occurred in the GVP group of aflibercept and ranibizumab (0.052%) compared with 24 in the PFS group (0.017%). There was no difference in the endophthalmitis rates with or without universal masking (RR, 0.953; 95% CI 0.616-1.473, P = .91). Discussion: PFS use was associated with a significant reduction in the rate of endophthalmitis while the use of surgical face masks did not appear to significantly impact the rate of endophthalmitis.

Risk Factors for the Development of Fellow Eye Horseshoe Retinal Tears Following Horseshoe Retinal Tear in the Presenting Eye.

BACKGROUND: This study investigated factors associated with fellow eye horseshoe retinal tear (HST) development in consecutive patients with a presenting eye HST. MATERIALS AND METHODS: Medical records were reviewed for patients with initial HSTs between 2015 and 2017 and 24 factors were analyzed. Logistic regression was used to assess factors associated with fellow eye HST development. RESULTS: In total, 242 patients with an HST were identified with mean follow-up of 68.3 months. Four associations with fellow eye HST development were identified: (1) presence of fellow eye lattice degeneration, (2) subsequent presenting eye HSTs, (3) fellow eye vitreous hemorrhage at presenting eye HST occurrence, (4) OCT-determined stage 3 fellow eye posterior vitreous detachment at presenting eye HST occurrence. CONCLUSION: Four clinical findings associated with fellow eye HST development following presenting eye HST were identified. These factors may be important considerations during management patients with HST. [Ophthalmic Surg Lasers Imaging Retina 2023;54:338-345.].

Demographic and Socioeconomic Factors in Prospective Retina-Focused Clinical Trial Screening and Enrollment.

Historically marginalized populations are disproportionately affected by many diseases that commonly affect the retina, yet they have been traditionally underrepresented in prospective clinical trials. This study explores whether this disparity affects the clinical trial enrollment process in the retina field and aims to inform future trial recruitment and enrollment. Age, gender, race, ethnicity, preferred language, insurance status, social security number (SSN) status, and median household income (estimated using street address and zip code) for patients referred to at least one prospective, retina-focused clinical trial at a large, urban, retina-based practice were retrospectively extracted using electronic medical records. Data were collected for the 12-month period from 1 January 2022, through 31 December 2022. Recruitment status was categorized as Enrolled, Declined, Communication (defined as patients who were not contacted, were contacted with no response, were waiting for a follow-up, or were scheduled for screening following a clinical trial referral.), and Did Not Qualify (DNQ). Univariable and multivariable analyses were used to determine significant relationships between the Enrolled and Declined groups. Among the 1477 patients, the mean age was 68.5 years old, 647 (43.9%) were male, 900 (61.7%) were White, 139 (9.5%) were Black, and 275 (18.7%) were Hispanic. The distribution of recruitment status was: 635 (43.0%) Enrolled, 232 (15.7%) Declined, 290 (19.6%) Communication, and 320 (21.7%) DNQ. In comparing socioeconomic factors between the Enrolled and Declined groups, significant odds ratios were observed for age (p < 0.02, odds ratio (OR) = 0.98, 95% confidence interval (CI) [0.97, 1.00]), and between patients who preferred English versus Spanish (p = 0.004, OR = 0.35, 95% CI [0.17, 0.72]. Significant differences between the Enrolled and Declined groups were also observed for age (p < 0.05), ethnicity (p = 0.01), preferred language (p < 0.05), insurance status (p = 0.001), and SSN status (p < 0.001). These factors may contribute to patient participation in retina-focused clinical trials. An awareness of these demographic and socioeconomic disparities may be valuable to consider when attempting to make clinical trial enrollment an equitable process for all patients, and strategies may be useful to help address these challenges.

Impact of Race and Ethnicity on Presentation and Surgical Outcomes of Idiopathic Macular Holes.

There is limited data on the presentation and surgical outcomes of idiopathic macular holes (IMH) for different ethnic and racial groups. Recognition of distinct, clinically-relevant patient subgroups may provide opportunities to identify specific unmet needs including possible barriers to optimal healthcare delivery. Medical records of patients who underwent surgery for IMH (between 2016 and 2022) at a large, urban retina practice were reviewed and self-reported ethnicity (Hispanic and non-Hispanic) and race (Asian, Black, White, and Other) were captured. The primary variables included (1) mean minimum linear diameter (MLD) at presentation and (2) surgical outcome (IMH closure status). Overall, mean MLD for all study eyes (515) was 366.1 µm, and surgical success was achieved in 489 (95.0%) eyes. Hispanic eyes presented with larger mean MLD (p = 0.002) compared to non-Hispanic eyes. Asian, Black, and Other eyes presented with larger mean MLD (p = 0.033, p < 0.001, p < 0.001) when compared to White eyes. The presentation of IMH varied in severity among different ethnic and racial groups. Hispanic patients were found to have worse preoperative visual acuity (VA), longer time to surgery, and larger mean MLD and BD compared to non-Hispanic participants. Black and Other patients were found to have worse VA, time to surgery, and larger mean MLD and BD when compared to White participants.

Outcomes of Eyes Undergoing Multiple Surgical Interventions after Failure of Primary Rhegmatogenous Retinal Detachment Repair.

PURPOSE: To assess outcomes among eyes undergoing surgery for recurrent rhegmatogenous retinal detachment (RRD) and investigate variables that correlate with visual and anatomic outcomes. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: Eyes in which initial RRD repair failed that underwent ≥2 surgeries for RRD repair between January 1, 2016, and December 31, 2020. METHODS: A retrospective analysis of eyes that underwent ≥2 RRD repairs. Eyes with etiologies of retinal detachment other than RRD, previous vitreoretinal surgery, and proliferative diabetic retinopathy were excluded. One-way analysis of variance with Tukey honestly significant difference testing and multivariate regression analyses were used to assess statistical significance. MAIN OUTCOME MEASURES: Anatomic success rate and habitual best recorded visual acuity (VA) at postoperative time intervals and at final follow-up. RESULTS: The single-operation success rate (SOSR) among eyes that underwent primary RRD repair over a 5-year period was 92.4% (2021 of 2187 eyes). The remaining 166 eyes (164 patients) in which primary RRD repair failed were included in this study. Although the anatomic success rates after the second and third RRD repairs were lower than the SOSR (71.7% and 68.1%, respectively), the final anatomic success rates did not significantly differ between eyes that underwent ≥2 RRD repairs (range, 90.6%-100%) (P > 0.05), and final anatomic success was achieved in 95.8% of the eyes. The average VA at both postoperative time intervals and final follow-up decreased with an increased total number of RRD repairs. Eyes that received silicone oil endotamponade during the second RRD repair were 20.3% (P = 0.03) and 38.4% (P = 0.04) less likely to require a third RRD repair compared with eyes that received octafluoropropane and sulfur hexafluoride gases, respectively. Eyes that developed a third RRD due to proliferative vitreoretinopathy (PVR) (n = 43) were 110% more likely to require a fourth RRD repair than eyes that developed a third RRD due to a new tear or failure to reattach (n = 4) (P = 0.04). CONCLUSIONS: In this series, the rates of anatomic success appeared consistent after each surgery when multiple reoperations were required for RRD. The VA decreased with an increased total number of RRD repairs, and the endotamponade choice might have affected the risk of additional reoperations. Proliferative vitreoretinopathy was a significant prognostic factor for RRD recurrence.

Molecular characterization and brain distribution of the progesterone receptor in whiptail lizards.

Progesterone and its nuclear receptor are critical in modulating reproductive physiology and behavior in female and male vertebrates. Whiptail lizards (genus Cnemidophorus) are an excellent model system in which to study the evolution of sexual behavior, as both the ancestral and descendent species exist. Male-typical sexual behavior is mediated by progesterone in both the ancestral species and the descendant all-female species, although the molecular characterization and distribution of the progesterone receptor protein throughout the reptilian brain is not well understood. To better understand the gene targets and ligand binding properties of the progesterone receptor in whiptails, we cloned the promoter and coding sequence of the progesterone receptor and analyzed the predicted protein structure. We next determined the distribution of the progesterone receptor protein and mRNA throughout the brain of Cnemidophorus inornatus and Cnemidophorus uniparens by immunohistochemistry and in situ hybridization. We found the progesterone receptor to be present in many brain regions known to regulate social behavior and processing of stimulus salience across many vertebrates, including the ventral tegmental area, amygdala, nucleus accumbens and several hypothalamic nuclei. Additionally, we quantified immunoreactive cells in the preoptic area and ventromedial hypothalamus in females of both species and males of the ancestral species. We found differences between both species and across ovarian states. Our results significantly extend our understanding of progesterone modulation in the reptilian brain and support the important role of the nuclear progesterone receptor in modulating sexual behavior in reptiles and across vertebrates.

Optical coherence tomography retinal nerve fiber layer analysis in eyes with long axial lengths.

PURPOSE: To evaluate the relationship between axial length (AL) and retinal nerve fiber layer (RNFL) profile and to characterize differences in optical coherence tomography RNFL of myopic glaucomatous eyes compared to nonglaucomatous eyes. METHODS: Retrospective chart review of 170 eyes of 89 subjects with optical biometry and optical coherence tomography RNFL assessment was conducted. RESULTS: Temporal RNFL thickness showed no association with AL in either glaucomatous or nonglaucomatous eyes. Nasal thinning was most strongly associated with glaucoma in myopic eyes. Both myopic glaucomatous and nonglaucomatous eyes had a mean RNFL thickness of 16-22 µm thinner than mean RNFL thickness of normal AL eyes. CONCLUSION: An average of 16-22 µm thinning of RNFL compared to nomogram can be tolerated in patients with long AL. Prominent nasal thinning likely represents changes from axial elongation. Temporal RNFL thinning in those with long AL tends to be mild, and significant thinning should raise suspicion for glaucoma.

A Case of Endophthalmitis After Bilateral Medial Rectus Recession.

A 9-month-old male infant with a history of Down syndrome underwent bilateral medial rectus recession. Two weeks postoperatively, he developed leukocoria of the left eye with a white opacity posterior to the lens, numerous undulations, necrosis, and hemorrhages in the retrolental space. His contralateral eye had white retinal lesions nasally. Ultrasound examination of the left eye showed a funnel retinal detachment, loculated debris, and a small, central, hyperechoic area concerning for calcification. He underwent enucleation because retinoblastoma could not be definitively ruled out. Given this patient's low visual potential, enucleation was a definitive and safe treatment option. Ocular pathology showed significant inflammation and necrosis. There was an area of scleral perforation by a suture adherent to the retina and vitreous, surrounded by inflammatory cells. This case uniquely demonstrates pediatric endophthalmitis following strabismus surgery, secondary to scleral perforation confirmed by histopathological analysis. Care must be taken during scleral passage of sutures to prevent inadvertent scleral perforation and the potential complication of endophthalmitis. [J Pediatr Ophthalmol Strabismus. 2017;54:e37-e41.].