Targeting the Tie-2 Receptor with Faricimab in Central Serous Chorioretinopathy: A Case Series Motivated by a Genetic Finding: Faricimab in central serous chorioretinopathy.

PURPOSE: To investigate the effects of faricimab, a bispecific antibody targeting VEGF and Ang-2 (thus increasing Tie-2 activity), in patients with CSC based on a recent genetic study that implicated Tie-2 signaling in CSC pathophysiology. DESIGN: A retrospective interventional multicenter case series. METHODS: We included patients with chronic CSC (persistent or recurrent SRF for ≥6 months) who received at least one faricimab 6mg injection between January 1 2022 and April 1 2024. Study sites included Massachusetts Eye and Ear and University of California San Francisco. Patients with evidence of a choroidal neovascular membrane on color photos, optical coherence tomography (OCT) and/or fluorescein angiography were excluded. 16 eyes (15 patients) met the inclusion criteria. The median central macular thickness at each visit from 52 weeks before to 52 weeks after the first faricimab injection was calculated using automated Heidelberg Spectralis ETDRS subfield measurements. RESULTS: Prior to treatment with faricimab, CSC had been diagnosed a median of 4.1 years (range 0.9-8) earlier and SRF (and intraretinal fluid [IRF] in a subset) had been continuously present for a median of 30 weeks (range 9-257). Decreases in macular thickness were observed in 14/16 eyes after the first faricimab injection and in 14/16 eyes in the full follow-up period compared with prior, 10 of which experienced complete resolution of SRF following the start of the first series of injections at a median of 4 weeks (range 2-25). One eye worsened after the second injection. The median improvement in macular thickness was 40µm [range -3 to 89.5] (P=0.0007). Upon review of OCT images, reductions in macular thickness were consistent with reductions in SRF and/or IRF. Visual acuity improved by 2 lines or more in 6/16 eyes. CONCLUSIONS: In a retrospective case series of patients with chronic CSC and longstanding SRF, we observed improvement in macular thickness after intravitreal faricimab. While the small number of patients and variable natural history of CSC preclude definitive conclusions, a randomized controlled trial seems warranted.

Novel heterozygous OPA3 variant in a family with congenital cataracts, sensorineural hearing loss and neuropathy, without optic atrophy and comparison of pathogenic and population variants.

Heterozygous mutations in the OPA3 gene are associated with autosomal dominant optic atrophy-3 (OPA3), whereas biallelic mutations cause autosomal recessive 3-methylglutaconic aciduria type III. To date, all cases with pathogenic variants in the gene OPA3 have presented with optic atrophy. We report a large family with congenital cataracts, hearing loss and neuropathy, with a likely pathogenic novel missense variant in OPA3, c.30G>C; p.(Lys10Asn) that segregates with disease in the family pedigree. The family's clinical presentation has significant phenotypic overlap with previously reported cases of OPA3, except for a notable lack of optic atrophy. The analysis of all known disease-associated variants in OPA3 revealed an enrichment in missense variants in patients with OPA3 phenotype compared with loss-of-function variants, which are more likely to be observed in individuals with 3-methylglutaconic aciduria type III, supporting different mechanisms of disease. This case broadens the clinical and genetic spectrum associated with OPA3 mutations and highlights that optic atrophy is not an obligate feature of OPA3-related disorders.

A survey of perceptions of exposure to new technology in residents and practicing ophthalmologists.

BACKGROUND: Incorporation of the rapid advances in ophthalmologic surgical and diagnostic techniques inherent in the field poses a challenge to residency training programs. This study investigates exposure to new technologies during residency and perception of its impact on practice patterns. METHODS: Ophthalmology residents at various training levels and practicing ophthalmologists who had completed their training were invited to participate in a survey study assessing exposure to various technologies in residency and in practice. Data collection occurred from December 2022 to June 2023. Descriptive statistics were performed. RESULTS: The study received 132 unique responses, including 63 ophthalmology residents and 69 practicing ophthalmologists. 65.2% (n = 45) of practicing ophthalmologists and 47.6% (n = 30) of current residents reported discussion/training on newly developed products on the market (e.g. premium IOLS, MIGS), was "minimally discussed but not emphasized" or "not discussed at all" in residency. 55.1% (n = 38) of practicing ophthalmologists reported that exposure to new technologies during residency did influence types of technologies employed during practice. The majority resident physicians reported enjoying being trained on newer technology and feeling more prepared for future changes in the field (95.2%, n = 60) and felt that having industry partnerships in residency enhances education and training (90.5%, n = 57). CONCLUSIONS: Considering how to maximize exposure to newer technologies/devices during residency training is important, and may contribute to training more confident, adaptable surgeons, who are more likely to critically consider new technologies and adopt promising ones into their future clinical practice.

Designing custom three-dimensional printed eyeglasses for children with frontonasal abnormalities: addressing challenges in access and fit.

Improving access to comfortable and well-fitting glasses for children with craniofacial differences may improve their visual outcomes. The purpose of this study was to describe challenges in spectacle fitting facing patients with frontonasal dysplasia and to report successful methods for creating custom 3D designed glasses. Additionally, the process of systematically collecting and analyzing spectacle-fitting challenges can inform future processes of automated design of 3D printed glasses and can be applied to other specific craniofacial syndromes.

AGE-RELATED MACULAR DEGENERATION INJECTION FREQUENCY: Effects of Distance Traveled and Travel Support.

PURPOSE: Although efficacious, intravitreal anti-vascular endothelial growth factor therapy regimens for neovascular age-related macular degeneration can prove difficult for patients to adhere to because of high cost and burden of transportation. METHODS: Analysis of electronic health record data from the San Francisco Veterans Administration Medical Center eye clinic (January 1, 2010 to December 31, 2019) was performed, extracting demographic data, anti-vascular endothelial growth factor injection history, and enrollment in the SFVA travel benefit program. Two-tailed P -values were calculated for Poisson regression examining average number of injections per year as the outcome and distance traveled as the primary predictor. Travel benefit was evaluated as a modifying effect on the distance-injection relationship. RESULTS: Three hundred and eighteen patients who received intravitreal injection for treatment of neovascular age-related macular degeneration were included in the analysis. Median (interquartile range) distance to clinic was 31.5 miles (7.4-69.4 miles). Driving distance in miles was inversely associated with average number of injections per year. Among all 318 patients, for every additional 100 miles a patient lived from our clinic, the patient received on average 2.5 fewer injections per year ( distance = -0.0025, P < 0.001), but this was not the case for patients with travel benefits ( distance = -0.0011, P = 0.362). CONCLUSION: The greater the distance from a patient's eye clinic, the lower the average number of injections per year. However, travel benefits mitigated this relationship, highlighting opportunities for improving patient's adherence through assistance programs.

NOVEL METHOD FOR VISUALIZING PERIPHERAL RETINAL STRUCTURES WITH MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY.

BACKGROUND/PURPOSE: Visualization of peripheral retinal structures with optical coherence tomography (OCT) can be challenging but can offer valuable clinical information. We describe a method for intraoperative OCT of the peripheral retina. METHODS: An investigational microscope-integrated OCT system with real-time 4D volumetric imaging was used in conjunction with a Goldmann style mirrored contact lens intraoperatively to capture peripheral images in three patients. RESULTS: We identified retinoschisis, a retinal break, and areas of focal retinal detachment using our peripheral OCT method. CONCLUSION: Use of a Goldmann lens in conjunction with intraoperative OCT offers surgeons the ability to resolve peripheral pathology that cannot be easily evaluated with OCT otherwise.

Bilateral Hypopyon in a Young Woman.

A 28-year-old woman presented to the emergency department with a 5-day history of bilateral blurry vision, eye redness, discharge, photophobia, and pain. There were more than 20 cells per high-power field of 1 mm × 1 mm beam, with fibrin bilaterally and 2.5-mm hypopyon in the right eye and 2.7-mm hypopyon in the left eye. What would you do next?

DELAYED ONSET Cutibacterium (FORMERLY Propionibacterium ) acnes ENDOPHTHALMITIS TRIGGERED BY INTRAVITREAL STEROID INJECTION.

PURPOSE: We report a case of delayed onset Cutibacterium acnes ( C. acnes , formerly Propionibacterium acnes or P. acnes ) endophthalmitis with the onset triggered by intravitreal steroid injection (triamcinolone acetonide) in a pseudophakic patient, 7 years after cataract surgery. METHODS/PATIENTS: A 67-year-old man presented with gradual worsening of vision, eye redness, and photosensitivity that started a month after intravitreal triamcinolone acetonide injection (Triescience, 4 mg/0.1 mL, Alcon Labs, Fort Worth, TX) for cystoid macular edema secondary to branch retinal vein occlusion in the right eye. The patient had undergone cataract surgery with intraocular lens in that eye 7 years prior. Examination showed the visual acuity of counting fingers at 3 feet and conjunctival injection, with 2+ anterior chamber cell and 2+ vitreous haze. Uveitis work up including angiotensin-converting enzyme, QuantiFERON Gold, and syphilis IgG screen was negative. Diagnostic pars plana vitrectomy with intravitreal injection of antibiotics was performed, and vitreous sample was sent for detailed laboratory analysis. RESULTS: Vitreous fluid analysis was positive for C. acnes and negative for viral, fungal, and malignant cells. Although the patient received intravitreal antibiotics injection twice, the intraocular infection and inflammation persisted which eventually required an intraocular lens and capsular bag removal, followed by insertion of a secondary intraocular lens later. CONCLUSION: Delayed onset C. acnes endophthalmitis may be triggered by an intravitreal steroid injection in pseudophakic patients.

Time and Distance Cost of Longer Acting Anti-VEGF Therapies for Macular Degeneration: Contributions to Drug Cost Comparisons.

Purpose: To evaluate the holistic cost of longer acting anti-VEGF therapy for macular degeneration when considering the associated costs of travel to the retina clinic. Design: Theoretical evaluation of cost using publicly available pricing data and reimbursements at the Veterans Affairs (VA) Medical Center. Patients and Methods: Setting: VA Medical Center. Study population: Patients with age related macular degeneration. Main outcome measures: Three-year cost of therapy when considering medication as well as travel costs and time spent in transit. Results: Based on cost data derived purely from wholesale acquisition cost and projected injection frequency over the first three years of treatment, faricimab is less expensive than ranibizumab and aflibercept by $37,709 and $6359, respectively. Aflibercept is less expensive ranibizumab by $31,350 over the first 3 years of treatment. When considering even small distances traveled by patients, these cost differences grow, amplified at even larger distances: at 25 miles, ranibizumab becomes $38,814 and $32,133 more expensive than faricimab and aflibercept, respectively. Aflibercept becomes $6681 more expensive than faricimab. At 100 miles, ranibizumab becomes $41,502 and $34,038 more expensive than faricimab and aflibercept, respectively. Aflibercept becomes $7464 more expensive than faricimab. Conclusion: Longer acting anti-VEGF therapies may differ not only in their wholesale acquisition cost, but also in the frequency of per label injections and associated clinic visits. Taking into account distance and time cost of travel may contribute to a more holistic view of cost differences among these therapies.

Using a Smartphone 3-Dimensional Surface Imaging Technique to Manufacture Custom 3-Dimensional-Printed Eyeglasses.

Importance: Finding a suitable fit in glasses for pediatric patients with congenital and acquired craniofacial abnormalities is difficult; consequently, these children are at high risk of vision loss secondary to refractive amblyopia as they often have poor adherence to daily glasses wearing. Custom 3-dimensional (3D)-printed glasses may have an improved design and fit, but access is limited by the availability of computed tomography and magnetic resonance imaging (MRI). Objective: To describe a method for using a commercially available smartphone 3D surface imaging (3DSI) technique to capture facial anatomy as a basis for custom glasses design. Design, Setting, and Participants: This quality improvement study analyzes data from a case series in a primary academic center with multiple referral centers throughout the United States. The evaluation included reported fit descriptions from patients with poor glasses adherence due to craniofacial abnormalities. Main Outcomes and Measures: Key anatomic parameters for glasses fit (face width, distance from ear bridge to nasal bridge, distance from center of pupil to center of nasal bridge, distance from lateral to medial canthus, ear vertical offset, and nasal bridge width) were compared between scans. A 3DSI scan was considered successful if these key parameters could be determined and the difference in measurements was less than 5% between MRI and 3DSI. A second outcome measure included the fit of glasses designed by the 3DSI method as reported by the patient, parent, or guardian. Results: Measurements of key parameters for glasses fit were similar across MRI and 3DSI scans with a mean (SD) difference of 1.47 (0.79) mm between parameters (range, 0.3-4.60 mm). Among 20 patients aged 1 to 17 years with craniofacial abnormalities, all achieved a successful fit (reporting daily glasses adherence without irritation) as judged by the patient, parent, or guardian. A mean of 1.7 revisions were made from initial prototype to final frame production using 3DSI technology. Conclusions and Relevance: This study demonstrated that smartphone-enabled 3DSI coupled with widely available 3D printing technology can produce custom frames with a successful fit for patients with craniofacial anomalies. This accessible and well-tolerated imaging process may have implications for adherence with glasses wearing among patients at risk of vision loss due to amblyopia.

Endogenous Methicillin-Resistant Staphylococcus Aureus (MRSA) Endophthalmitis: A Six-year Series at a Tertiary Care Center.

PURPOSE: To investigate the clinical outcomes of methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis. METHODS: Clinical courses were reviewed for 17 eyes (15 patients) with endogenous MRSA endophthalmitis based on positive blood and vitreous culture or clinical suspicion between 2013 to 2019 at Duke University Hospitals. RESULTS: Of 17 eyes, initial VA ranged from 20/40 to light perception. Of 15 patients, 9 had predisposing risk factors for bacteremia. All eyes received intravitreal vancomycin, 13 also received ceftazidime, and 2 also received amikacin instead of ceftazidime. Nine eyes developed retinal detachment; 6 underwent vitrectomy. Final VA ranged from 20/20 to no light perception and was ≥20/200 in 8 eyes. Eleven eyes had improved VA, 2 eyes were unchanged, and 4 were worse. CONCLUSIONS: This study is the largest series on endogenous MRSA endophthalmitis to date. Patients had a higher proportion of final VA ≥20/200, similarly high rate of RD, and fewer enucleations compared to prior reports.

A novel three-dimensional printed device to improve the safety of trocar insertion in hypotonous eyes.

The force required for trocar insertion in hypotonous eyes can cause significant deformation of the globe and result in an iatrogenic injury to the lens, posterior capsule, or retina from the sharp trocar tip. We developed a device designed to stabilize the globe and provide counterpressure without significant globe deformation during trocar insertion. Our novel device was modeled using computer-aided design software, three-dimensional (3D) printed, and validated in an ex vivo porcine model. The risk of trocar-retinal touch was evaluated by comparing the distance between the trocar tip and opposing retina with either a cotton swab or our 3D printed device. We found an increased distance between the retina and trocar tip at the time of trocar insertion using our novel device: 3.3 ± 1.3 mm (P = 0.035), suggesting an improved safety margin. This device has the potential to improve the safety of trocar insertion in eyes at risk of trocar-associated injury, including hypotonous, previously vitrectomized, and nanophthalmic eyes.

Development, Validation, and Innovation in Ophthalmic Laser-Based Imaging: Report From a US Food and Drug Administration-Cosponsored Forum.

In April 2019, the US Food and Drug Administration, in conjunction with 11 professional ophthalmic, vision science, and optometric societies, convened a forum on laser-based imaging. The forum brought together the Food and Drug Administration, clinicians, researchers, industry members, and other stakeholders to stimulate innovation and ensure that patients in the US are the first in the world to have access to high-quality, safe, and effective medical devices. This conference focused on the technology, clinical applications, regulatory issues, and reimbursement issues surrounding innovative ocular imaging modalities. Furthermore, the emerging role of artificial intelligence in ophthalmic imaging was reviewed. This article summarizes the presentations, discussion, and future directions.

Aphakic contact lens use for improved handheld optical coherence tomography imaging in pediatric aphakic patients.

Handheld optical coherence tomography (OCT) makes it possible to acquire intraoperative and clinical imaging in infants and children for whom standard OCT is not possible. In patients with a retinal pathology who are left aphakic after surgery, however, image clarity is affected by insufficient refractive correction with handheld OCT. We describe a technique for supplementing the refractive power of the handheld OCT device with an aphakic contact lens to improve image clarity.

Management of a rhegmatogenous retinal detachment in a pregnant patient.

PURPOSE: To describe the management of a rhegmatogenous retinal detachment (RRD) in a pregnant patient. OBSERVATIONS: A 30-year-old, 26-week pregnant female presented with curtain vision loss in the left eye. Exam findings were significant in the left eye for an inferior fovea-sparing RRD. Care was coordinated and discussed with anesthesia and OB/GYN. The patient underwent surgery with monitored anesthesia care and a 41 scleral buckle, cryotherapy and C3F8 gas. The retina remained attached at 4 months post-operatively. A healthy girl was delivered via spontaneous vaginal delivery at 39 weeks. CONCLUSION: Safe and successful treatment of RRD in pregnant patients can be achieved with careful coordination between ophthalmology, anesthesia, and obstetrics. An understanding of pregnancy specific considerations is important in order to optimize patient outcomes.