Comparison of Blue-Light Autofluorescence and Ultrawidefield Green-Light Autofluorescence for Assessing Geographic Atrophy.

PURPOSE: The goal of this study was to evaluate and compare the intermodality and interreader agreement of manual and semiautomated geographic atrophy (GA) area measurements in eyes with GA due to age-related macular degeneration (AMD) using conventional blue-light fundus autofluorescence (FAF) and ultrawidefield (UWF) green-light FAF systems. DESIGN: Prospective Cohort Study. SUBJECTS: Seventy-two eyes of 50 patients with a diagnosis of advanced nonneovascular AMD with GA. METHODS: Fundus autofluorescence images of eyes with GA were obtained during a single visit using both the Spectralis HRA + OCT2 device and the Optos California device. The area of the GA lesion(s) was segmented and quantified (mm2) with a fully manual approach where the lesions were outlined using Optos Advance and Heidelberg Eye Explorer (HEYEX) software. In addition, for the Heidelberg blue FAF images, GA lesions were also measured using the instrument's semiautomated software (Region Finder 2.6.4). For comparison between modalities/grading method, the mean values of the 2 graders were used. Intraclass correlation coefficients were computed to judge the agreement between graders. RESULTS: Seventy-two eyes of 50 patients were included in this study. There was nearly perfect agreement between graders for the measurement of GA area for all 3 modalities (intraclass correlation coefficient: 0.996 for manual Optos Advance, 0.996 for manual Heidelberg HEYEX, and 0.995 for Heidelberg Region Finder). The measurement of GA area was strongly correlated between modalities, with Spearman correlation coefficients of 0.985 (P < 0.001) between manual Heidelberg and manual Optos, 0.991 (P < 0.001) for Region Finder versus manual Heidelberg, and 0.985 (P < 0.001) for Region Finder versus manual Optos. The absolute mean area differences between the Heidelberg manual versus Region Finder, manual Optos versus Region Finder, and manual Optos versus manual Heidelberg were 1.61 mm2 (P < 0.001), 0.90 mm2 (P < 0.006), and 0.71 mm2 (P < 0.001), respectively. CONCLUSIONS: We observed excellent interreader agreement for measurement of GA using either 30-degree blue-light FAF or UWF green-light FAF, establishing the reliability of UWF imaging for macular GA assessment. Although the absolute measurements between devices were strongly correlated, they differed significantly, highlighting the importance of using the same device for a given patient for the duration of a study. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The real-world efficacy and safety of faricimab in neovascular age-related macular degeneration: the TRUCKEE study - 6 month results.

BACKGROUND/OBJECTIVE: Investigate real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). SUBJECTS/METHODS: Multicenter, retrospective chart review was conducted on patients treated with faricimab for nAMD from February 2022 to September 2022. Collected data includes background demographics, treatment history, best-corrected visual acuity (BCVA), anatomic changes, and adverse events as safety markers. The main outcome measures are changes in BCVA, changes in central subfield thickness (CST) and adverse events. Secondary outcome measures included treatment intervals and presence of retinal fluid. RESULTS: After one injection of faricimab, all eyes (n = 376), previously-treated (n = 337) and treatment-naïve (n = 39) eyes demonstrated a + 1.1 letter (p = 0.035), a + 0.7 letter (p = 0.196) and a + 4.9 letter (p = 0.076) improvement in BCVA, respectively, and a - 31.3 µM (p < 0.001), a - 25.3 µM (p < 0.001) and a - 84.5 µM (p < 0.001) reduction in CST, respectively. After three injections of faricimab, all eyes (n = 94), previously-treated (n = 81) and treatment-naïve (n = 13) eyes demonstrated a + 3.4 letter (p = 0.03), a + 2.7 letter (p = 0.045) and a + 8.1 letter (p = 0.437) improvement in BCVA, and a - 43.4 µM (p < 0.001), a - 38.1 µM (p < 0.001) and a - 80.1 µM (p < 0.204) reduction in CST, respectively. One case of intraocular inflammation was observed after four injections of faricimab and resolved with topical steroids. One case of infectious endophthalmitis was treated with intravitreal antibiotics and resolved. CONCLUSIONS: Faricimab has demonstrated improvement or maintenance of visual acuity for patients with nAMD, along with rapid improvement of anatomical parameters. It has been well-tolerated with low incidence of treatable intraocular inflammation. Future data will continue to investigate faricimab for real-world patients with nAMD.

Expanded Clinical Spectrum of Pentosan Polysulfate Maculopathy: A Macula Society Collaborative Study.

PURPOSE: Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings. DESIGN: Multi-institutional retrospective study. PARTICIPANTS: Patients exhibiting findings suggestive of PPS maculopathy identified from April 30, 2019, to December 4, 2020. METHODS: Members of the Macula Society submitted cases of presumed PPS maculopathy for consideration in this series. Diagnosis was confirmed by masked review of fundus imaging. Clinical characteristics of confirmed cases were summarized with descriptive statistics. MAIN OUTCOME MEASURES: Pentosan polysulfate exposure characteristics and fundus imaging features. RESULTS: There were 74 patients with PPS maculopathy included in the current study. Median (interquartile range) age at diagnosis was 62.0 years (56.0-65.8). The median duration of exposure to PPS was 14.0 years (10.2-18.9), with a median cumulative exposure of 1.5 kg (0.9-2.4). The most common presenting symptom was decreased or blurry vision (66.2%), followed by prolonged dark adaption or nyctalopia (32.4%). The most common referral diagnosis was age-related macular degeneration (54.1%); 16.2% of patients were referred for suspected PPS maculopathy. Novel imaging findings emerged, including highly asymmetric disease in 2 patients and a prominent vitelliform maculopathy in 2 patients. CONCLUSIONS: Most patients with PPS maculopathy exhibit characteristic findings on multimodal fundus imaging in the setting of high cumulative exposure to the oral drug. Some patients in the current study manifested novel imaging findings, expanding our understanding of the phenotypic spectrum of this condition. We recommend considering standardized ophthalmic screening of patients treated with PPS.

Outcomes of small-gauge vitreoretinal surgery without scleral-depressed shaving of the vitreous base in the era of wide-angle viewing systems.

PURPOSE: To evaluate outcomes of small-gauge pars plana vitrectomy (PPV) for the treatment of rhegmatogenous retinal detachment (RD) without scleral-depressed shaving of the vitreous base. METHODS: Retrospective, consecutive case series. Surgical technique included small-gauge PPV (25G, 23G, 25G+ or 27G) and wide-angle vitrectomy viewing system in all cases. No cases were excluded based on the level of complexity of RD. Outcome measures were retinal reattachment rates and Snellen visual acuity (best-corrected visual activity [BCVA]). RESULTS: 312 eyes of 301 patients, mean age 60.8 years, and mean follow-up 23.1 months. Baseline characteristics included macula-off RD in 207 (66%) eyes, psudophakia in 124 (40%) eyes, high myopia in 74 (24%) eyes and giant retinal tear in 14 (5%) eyes. The retina was reattached with one procedure in 296 (95%) eyes. Final retinal reattachment was achieved in 310 (99%) eyes. The BCVA at baseline was >20/40 in 76 (24%) eyes, 20/50-20/100 in 48 (15%) eyes, 20/200-20/400 in 46 (15%) eyes and <20/400 in 142 (46%) eyes. At the last follow-up, the BCVA was >20/40 in 168 (54%) eyes, 20/50-20/100 in 60 (19%) eyes, 20/200-20/400 in 49 (16%) eyes and <20/400 in 35 (11%) eyes. The mean change in logMAR equivalent was -0.12 for the macula-on group and -1.13 for the macula-off group (p<0.0001). CONCLUSION: Small-gauge PPV without scleral-depressed vitreous base shaving can be associated with good anatomical and visual outcomes. Case selection based on the complexity of RD may not be required when considering small-gauge PPV.

Determining the effect of low-dose isotretinoin on proliferative vitreoretinopathy: the DELIVER trial.

PURPOSE: To examine the effect of low-dose, oral isotretinoin in lowering the risk of proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (RRD) repair. METHODS: Prospective, open label, dual-cohort study with pathology-matched historical controls. The prospective experimental arms included two cohorts, composed of 51 eyes with recurrent PVR-related RRD and 58 eyes with primary RRD associated with high-risk features for developing PVR. Eyes in the experimental arms received 20 mg of isotretinoin by mouth once daily for 12 weeks starting the day after surgical repair. The primary outcome measure was single surgery anatomical success rate at 3 months following the study surgery. RESULTS: The single surgery anatomic success rate was 78.4% versus 70.0% (p=0.358) in eyes with recurrent PVR-related retinal detachment exposed to isotretinoin versus historical controls, respectively. In eyes with RRD at high risk for developing PVR, the single surgery success rate was 84.5% versus 61.1% (p=0.005) for eyes exposed to isotretinoin versus historical controls, respectively. For eyes enrolled in the experimental arms, the most common isotretinoin-related side effects were dry skin/mucus membranes in 106 patients (97.2%), abnormal sleep/dreams in 4 patients (3.7%) and fatigue in 3 patients (2.8%). CONCLUSION: The management and prevention of PVR is challenging and complex. At the dose and duration given in this study, oral istotretinoin may reduce the risk of PVR-associated recurrent retinal detachment in eyes with primary RRD at high risk of developing PVR.

Ranibizumab Treatment for Pigment Epithelial Detachment Secondary to Neovascular Age-Related Macular Degeneration: Post Hoc Analysis of the HARBOR Study.

PURPOSE: To analyze the effect of baseline presence and height of pigment epithelial detachments (PEDs) on visual and anatomic outcomes at 24 months in patients with neovascular age-related macular degeneration (AMD) treated with ranibizumab. DESIGN: Post hoc analysis of HARBOR, a 24-month, phase III, randomized, multicenter, double-masked, active treatment-controlled study (clinicaltrials.gov identifier, NCT00891735). PARTICIPANTS: One thousand ninety-seven patients with neovascular AMD. METHODS: Intravitreal ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN) after 3 monthly loading doses. MAIN OUTCOME MEASURES: We evaluated the effect of presence and height of baseline PED on several outcomes at 24 months, including best-corrected visual acuity (BCVA), change in PED height, resolution of PED, and number of injections in the PRN arms. Development of macular atrophy at month 24 by presence or absence of PED was evaluated. RESULTS: Five hundred ninety-eight (54.5%) patients showed PED at baseline. In the ranibizumab 0.5-mg PRN group, mean numbers of injections were similar for patients with PED present or absent at baseline (14.0 vs. 12.5). Mean BCVA gains from baseline to 24 months were seen in all treatment groups and were comparable in patients with or without PED at baseline treated with ranibizumab 0.5 mg monthly (PED present at baseline, +9.0 letters; PED absent at baseline, +11.3 letters), 0.5 mg PRN (present, +8.4; absent, +7.9), 2.0 mg monthly (present, +7.1; absent, +11.1), or 2.0 mg PRN (present, +7.2; absent, +8.8). When analyzed by baseline PED height, mean BCVA gains were demonstrated and comparable in all treatment groups at 24 months except for patients treated with ranibizumab 2.0 mg monthly in the extra-large group (PEDs ≥352 µm; mean BCVA change, -0.8 letters). At 24 months, 53.2% (0.5 mg monthly), 44.5% (0.5 mg PRN), 70.4% (2.0 mg monthly), and 57.3% (2.0 mg PRN) of patients showed complete resolution of PED. CONCLUSIONS: Ranibizumab 0.5 mg given monthly or PRN effectively treated PEDs in patients with neovascular AMD, and significant vision gains resulted regardless of PED status and height at baseline. In this analysis, there was no additional vision benefit with a higher dose of ranibizumab (2.0 mg).

The Treatment Paradigm for the Implantable Miniature Telescope.

Advanced or end-stage age-related macular degeneration (AMD) results in significant visual impairment and a substantially reduced quality of life for patients. Therapeutic options for people with bilateral moderate or profound vision loss caused by end-stage AMD are limited. Although medical treatment capable of reversing the functional vision loss that results from end-stage AMD is non-existent, there are now treatments that can reverse some of that functional vision loss, including the implantable miniature telescope (IMT). This review article discusses the science behind the IMT, evaluates the data from clinical studies, and weighs the pros and cons of the technology.

Leukemia presenting as serous retinal detachment.

BACKGROUND: To describe a patient who presented with bilateral serous retinal detachments without the other retinal vascular or ocular inflammatory signs, and who was ultimately diagnosed with acute leukemia. METHODS: Case report and review of the literature. RESULTS: This patient presented with isolated bilateral serous retinal detachments as the initial manifestation of hematologic malignancy. CONCLUSION: Acute leukemia may present with serous retinal detachments without the signs of other retinopathy or ocular inflammation. Incorrect diagnosis may delay detection and proper management of the malignancy. Leukemia should be considered in the differential diagnosis of isolated serous retinal detachments.

Pars plana vitrectomy and scleral buckle versus pars plana vitrectomy alone for patients with rhegmatogenous retinal detachment at high risk for proliferative vitreoretinopathy.

PURPOSE: To compare using pars plana vitrectomy (PPV) combined with a scleral buckle versus primary vitrectomy alone in patients with rhegmatogenous retinal detachment at high risk for postoperative proliferative vitreoretinopathy (PVR). METHODS: Six hundred and seventy-eight patients were identified from billing data as having rhegmatogenous retinal detachment between April 1, 2010 and August 1, 2012. Patients were considered at high risk for PVR if they presented with retinal detachment in 2 or more quadrants, retinal tears >1 clock hour, preoperative PVR, or vitreous hemorrhage. RESULTS: Of the 678 patients with rhegmatogenous retinal detachment, 65 were identified as high risk for PVR. Thirty-six patients were treated with simultaneous PPV-scleral buckle and 29 patients were treated with PPV alone, with an overall success rate of 63.1%. The use of PPV-scleral buckle was associated with significantly higher single surgery anatomical success compared with patients treated with PPV alone (odds ratio, 3.24; 95% confidence interval, 1.12-9.17; P = 0.029). Visual acuity at 3 months postprocedure or final follow-up was no different between the treatment groups. Overall, 23.1% of patients developed postoperative PVR with no difference between surgical approaches. CONCLUSION: For patients at high risk for PVR, PPV-scleral buckle was associated with significantly higher rates of anatomical success compared with PPV alone.

Effect of topical aqueous suppression on intraocular gas duration after pure perfluoropropane injection in nonvitrectomized eyes with retinal detachment.

PURPOSE: To determine whether topical aqueous suppressants affect the duration of pure expansile intraocular gas in nonvitrectomized eyes. METHODS: A prospective randomized controlled trial was performed on nonvitrectomized patients undergoing retinal detachment repair with scleral buckle or pneumatic retinopexy using 0.3 mL of 100% perfluoropropane (C3F8) gas tamponade. Eyes were randomly assigned to receive topical dorzolamide 2% and timolol 0.5% twice daily postoperatively until gas dissolution or to observation. RESULTS: Twenty-one patients met all inclusion and exclusion criteria. Twelve were randomized to the control group and nine to the dorzolamide-timolol group. In the dorzolamide-timolol group, mean intraocular pressure was 17.4 on postoperative Day 1 and 12.5 on postoperative Week 1 (P = 0.03). In the control group, mean intraocular pressure was 14.5 on postoperative Day 1 and 15.1 on postoperative Week 1 (P = 0.73). The mean duration of C3F8 was 37.8 days in the dorzolamide-timolol group and 40.4 days in the control group (P = 0.70). CONCLUSION: Topical aqueous suppression does not seem to have a significant effect on the duration of pure expansile intraocular C3F8 in nonvitrectomized eyes after pneumatic retinopexy or scleral buckling.

Drug-induced uveitis.

PURPOSE OF REVIEW: Although more than 50% of all uveitis cases have no identifiable cause, certain medications can cause ocular inflammation and are often overlooked. Drug-induced ocular inflammation has increased in frequency with the advent of new bisphosphonates, antitumor necrosis factor biologic agents, and intravitreal triamcinolone and antivascular endothelial growth factor medications. Identification of these inciting drugs will simplify work-up and management of patients with uveitis and improve visual outcomes. RECENT FINDINGS: This review briefly focuses on the drugs that have long been known to be strongly associated with uveitis and emphasize new observations about these associations. It will also highlight the newest medications associated with uveitis and scleritis. The strength of the association between each drug and uveitis will be quantified and categorized into definite, probable, possible, and unlikely causes of uveitis utilizing Naranjo's classification criteria. SUMMARY: Drug-induced uveitis has become increasingly recognized in association with a number of commonly used systemic, intraocular, and topical medications. A detailed history is often all that is needed to identify these important, often overlooked, and readily curable causes of uveitis. Most cases of drug-induced uveitis respond promptly to discontinuation of the suspected agent in conjunction with topical corticosteroid and cycloplegic therapy.

Drug-induced uveitis.

A number of medications have been associated with uveitis. This review highlights both well-established and recently reported systemic, topical, intraocular, and vaccine-associated causes of drug-induced uveitis, and assigns a quantitative score to each medication based upon criteria originally described by Naranjo and associates.

CMV retinitis screening and treatment in a resource-poor setting: three-year experience from a primary care HIV/AIDS programme in Myanmar.

BACKGROUND: Cytomegalovirus retinitis is a neglected disease in resource-poor settings, in part because of the perceived complexity of care and because ophthalmologists are rarely accessible. In this paper, we describe a pilot programme of CMV retinitis management by non-ophthalmologists. The programme consists of systematic screening of all high-risk patients (CD4 <100 cells/mm3) by AIDS clinicians using indirect ophthalmoscopy, and treatment of all patients with active retinitis by intravitreal injection of ganciclovir. Prior to this programme, CMV retinitis was not routinely examined for, or treated, in Myanmar. METHODS: This is a retrospective descriptive study. Between November 2006 and July 2009, 17 primary care AIDS clinicians were trained in indirect ophthalmoscopy and diagnosis of CMV retinitis; eight were also trained in intravitreal injection. Evaluation of training by a variety of methods documented high clinical competence. Systematic screening of all high-risk patients (CD4 <100 cells/mm3) was carried out at five separate AIDS clinics throughout Myanmar. RESULTS: A total of 891 new patients (1782 eyes) were screened in the primary area (Yangon); the majority of patients were male (64.3%), median age was 32 years, and median CD4 cell count was 38 cells/mm3. CMV retinitis was diagnosed in 24% (211/891) of these patients. Bilateral disease was present in 36% of patients. Patients with active retinitis were treated with weekly intravitreal injection of ganciclovir, with patients typically receiving five to seven injections per eye. A total of 1296 injections were administered. CONCLUSIONS: A strategy of management of CMV retinitis at the primary care level is feasible in resource-poor settings. With appropriate training and support, CMV retinitis can be diagnosed and treated by AIDS clinicians (non-ophthalmologists), just like other major opportunistic infections.

The dexamethasone drug delivery system: indications and evidence.

INTRODUCTION: The Ozurdex(®) (Allergan Inc., Irvine, CA, USA) dexamethasone drug delivery system (DDS) was recently developed as a biodegradable intravitreal implant to provide sustained delivery of 700 µg of preservativefree dexamethasone to the retina and vitreous, and is approved by the United States Food and Drug Administration (FDA) for the treatment of macular edema associated with retinal vein occlusion, as well as for noninfectious posterior uveitis. This review summarizes the rationale behind the development of the dexamethasone DDS, evidence for its use in various clinical scenarios, and compares its efficacy to other available treatment options. METHODS: Published data regarding the dexamethasone DDS as well as unpublished data that has been presented at national meetings were reviewed. RESULTS: The dexamethasone DDS has evidence for efficacy in multiple clinical situations, including macular edema associated with retinal vein occlusion (RVO), macular edema associated with uveitis or Irvine-Gass syndrome, diabetic macular edema in vitrectomized eyes, persistent macular edema, noninfectious vitritis, and as adjunctive therapy for age-related macular degeneration. Safety concerns include cataract formation and intraocular pressure elevation that is most often temporary and amenable to medical management. CONCLUSIONS: The dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.

Update and review of central retinal vein occlusion.

PURPOSE OF REVIEW: To review the clinical picture of central retinal vein occlusion (CRVO), with an emphasis on recent therapeutic developments. RECENT FINDINGS: The most significant advances with regard to CRVO relate to the establishment of the important role of intravitreal anti-vascular endothelial growth factor and corticosteroids in the treatment of macular edema associated with vein occlusion. SUMMARY: Important objectives on evaluation of a patient presenting with a CRVO include differentiation between ischemic and nonischemic types, identification of any complications, and establishment of a treatment and/or follow-up plan. Macular edema is one of the main causes of vision loss in CRVO, and for the first time we can have effective treatment options for affected patients.