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OBJECTIVES: To describe conjunctiva and Tenon's capsule handling during the Port Delivery System with ranibizumab (PDS) implant insertion procedure including up-front assessments, planning, and instrumentation, with emphasis placed on the peritomy, scleral dissection, and closure steps. METHODS: Surgical pearls based on experience accumulated in the PDS clinical trial program in patients with retinal diseases. RESULTS: Preoperative preparation, specific instruments, and meticulous techniques are key to optimizing surgical outcomes. Before surgery, assessment of factors that affect conjunctival integrity and an in-office conjunctiva examination are conducted. Gentle, purposeful conjunctiva and Tenon's capsule handling with nontoothed forceps and suturing with a BV needle are recommended to prevent tissue damage. The peritomy is 6 mm by 6 mm, centered around the planned implant location in the superotemporal quadrant. A complete sub-Tenon's capsule dissection is achieved using a wide, robust lateral and posterior dissection technique to free tissue from the sclera and minimize tension. The globe is stabilized during scleral cutdown by grasping the sclera with fine-toothed forceps away from the incision edge to prevent tissue delamination. When closing the peritomy, both the conjunctiva and Tenon's capsule are completely captured and sutured with scleral anchoring at the apex of the peritomy to help prevent conjunctival retraction and erosion. Mitigation and detection of adverse events is critical to successful surgical outcomes. CONCLUSIONS: The PDS implant insertion procedure is straightforward, but it requires planned preoperative preparation, specific instruments, and meticulous techniques. The surgical pearls described here offer insights for optimizing outcomes. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:266–273.]

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 p p 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 p p 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.

Purpose To evaluate the real-world utility of the ForeseeHome monitoring device (Notal Vision, Ltd., Tel Aviv, Israel) for the detection of conversion from intermediate age-related macular degeneration (iAMD) to neovascular AMD (nAMD) and to compare with results published by the Home Monitoring of the Eye (HOME) study. Design Retrospective analysis of electronic health records. Participants Eyes prescribed use of the ForeseeHome device across 4 retinal practices in the United States. Methods Usage information was collected from the online ForeseeHome portal for all eyes prescribed the device. For a predetermined subset of eyes, additional clinical information was collected through chart review and analyzed for clinical utility. Main Outcome Measures Frequency and length of use, number of eyes that used the device, number of eyes that established a baseline measurement, number of eyes that converted to nAMD, and number of alerts. Results Seven hundred seventy-five eyes of 448 patients were prescribed use of the ForeseeHome device. Six hundred forty-nine eyes (83.7%) used the device at least once; among this population, 478 (73.7%) established a baseline measurement. Patients who established a baseline measurement were significantly younger than those who did not (P Conclusions Compared with the prospective HOME study, the utility of the ForeseeHome device in the current analysis of clinical practice application was limited. A meaningful proportion of eyes never used the device or could not establish a baseline measurement. Overall frequency of use was low, and continuous use of the device decreased over time. A need exists for improvement in home monitoring technology for eyes with iAMD at risk of conversion to nAMD.

Purpose: We demonstrate that Crumbs homologue 1 ( CRB1) maculopathy should be considered in the differential of petaloid pigmentary changes in the macula of young children with good vision who may be asymptomatic. Methods: We report on 2 unrelated male patients presenting at a young age with decreased vision from a macular dystrophy due to biallelic CRB1 mutations. Results: In addition to a previously described pathogenic variant, Ile167Gly169del, 2 new pathogenic missense variants in CRB1, Thr745Met and Cys948Tyr, are reported here. Conclusions: Although CRB1 mutations have been more commonly described in retinitis pigmentosa and Leber congenital amaurosis, we demonstrate that mutations in CRB1 can cause a maculopathy in which initial features can resemble juvenile X-linked retinoschisis. We show that the accompanying macular edema is responsive to carbonic anhydrase inhibitors. With long-term follow-up for each case, we illustrate the natural history of CRB1 maculopathy based on clinical examination and diagnostic imaging.

Purpose: This work aimed to assess postoperative outcomes associated with relaxing parafoveal nasal retinotomy for refractory macular hole repair. Methods: This was a retrospective interventional study of patients with persistent or recurrent macular holes following 1 or more standard repair procedures with pars plana vitrectomy and internal limiting membrane peeling. Patients received an additional pars plana vitrectomy and relaxing parafoveal nasal retinotomy, followed by fluid-air and air-gas exchange. Key postoperative outcomes included the achievement of macular hole closure and changes in visual acuity from baseline. Results: Thirteen patients with refractory macular holes were included, with a median age of 65 years (range, 49-90 years). The aperture diameter of the 13 macular holes ranged from 180 to 799 µm (median, 538 µm). Vitrectomy and relaxing parafoveal nasal retinotomy were performed in all 13 eyes, and after a median follow-up of 12 months (range, 3-34 months), anatomical closure was achieved in 12 of 13 eyes (92.3%). Overall, visual acuity (mean ± SE) improved significantly from 1.20 ± 0.15 logMAR (approximate Snellen equivalent, 20/320) at baseline to 0.84 ± 0.11 logMAR (Snellen, ∼ 20/125) during postoperative follow-up ( P < .05). Central and paracentral scotomas were observed in 8 of 11 eyes with postoperative Humphrey visual field 10-2 and/or 24-2 data available. Conclusions: Relaxing parafoveal nasal retinotomy may be an effective method to promote anatomical closure and improve vision outcomes in patients with recalcitrant macular holes.

Here we present a case series of full thickness macular holes (FTMHs) that closed with topical medical therapy. We see this technique as a promising alternative to surgery, especially in small FTMHs with cystoid hydration.

Davis Bhagat,1 Breanne Kirby,1 Harit Bhatt,1,2 Rama Jager,1,2 Meena George,1,2 Veeral Sheth1,2 1University Retina and Macula Associates, Oak Forest, IL, USA; 2University of Illinois, Chicago, IL, USACorrespondence: Veeral ShethUniversity Retina and Macula Associates, 15947 W 127th St Suite E, Lemont, IL 60439, USATel/Fax +1 630 410 8357Email vsheth@gmail.comPurpose: To evaluate treatment-related preferences among patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).Patients and Methods: We conducted a prospective survey of patients with nAMD or DME treated at one of three US-based retina clinics. Prior to survey development, small focus groups with anti-VEGF-treated patients identified five treatment-related “attributes” considered important to those with nAMD or DME: vision outcomes, cost to the insurance provider, cost to the patient, frequency of treatment, and drug label status. Attributes were described using two to three “levels”, and hypothetical treatment profiles were generated by assigning one level to each attribute. Surveyed patients were asked to indicate their preference between two given treatment profiles for a total of eight pairwise comparisons. Discrete choice conjoint analysis was performed to estimate the relative importance of each attribute for the overall patient cohort, and for subgroups stratified by age and highest education level.Results: Among 300 respondents, 54% were female, 78% were aged ≥ 65 years, and 67% indicated that high school was their highest level of education. Achieving good vision was the most important factor associated with anti-VEGF therapy for nAMD or DME (relative importance, 40.4%), followed by low cost to the patient, on-label drug status, less frequent treatment intervals, and low cost to the insurance provider (23.1%, 21.3%, 12.2%, and 3.0%, respectively). When patients were stratified by age group or highest education level, preference trends across subgroups were generally comparable with the overall cohort.Conclusion: Our data suggest that treatment decisions regarding anti-VEGF therapies for nAMD or DME are most likely driven by their efficacy, and that patients may be willing to accept less desirable treatment attributes, such as increased cost and/or injection frequency, in order to achieve superior vision outcomes.Keywords: anti-VEGF therapy, conjoint analysis, diabetic macular edema, neovascular age-related macular degeneration, patient preferences

PE firms supposedly create efficiencies through economies of scale, negotiate better contracts with payers, and standardize our practices with the end goal of helping us to provide more efficient patient care High-net-worth investors that think the stock market is overvalued or that are looking for alternative investments are investing their capital with PE firms 3 With interest rates being at all-time lows, these firms are also able to tap into the debt markets The PE firm's goal is to increase value by adding revenue, cutting costs, adding debt, and doing so in the shortest timeline possible 3 The average PE holding period for an investment like this is 5 6 years before they sell the practice and exit their investment 11 Although the younger physician may have had input on the initial sale and the PE firm that they would be working with, there is very little likelihood that they will have any input on who their next owner will be, which can have a negative impact on the practice culture and day-to-day experience for the physicians and their patients In the mid-1990s we saw physician practice management companies raise billions of dollars, purchase numerous physician practices, then go bankrupt 12 We could see a repeat scenario like this if PE shareholders see lower-than-expected returns (ie, from lower reimbursements) or a lack of secondary buyers for the groups the firms have collected (especially in context of the amount of debt taken on during these transactions)

In the United States, diabetic macular edema (DME) is the leading cause of vision loss among people with diabetic retinopathy. Despite the availability of different therapies for DME, up to half of patients with DME show some persistent edema after anti-vascular endothelial growth factor (VEGF) treatment alone, leaving these patients at high risk for vision loss. However, dosing in a similar fashion to that of pivotal anti-VEGF trials is difficult because of real-life challenges faced in clinical practice. This is particularly true for DME, in that the frequency and burden of anti-VEGF injections are a major challenge to patient care. Research evaluating anti-VEGF therapies has shaped the treatment paradigms for patients with DME, and similar benefits have also been noted in clinical trials evaluating the use of intravitreal steroids. Treatment with a long-term intravitreal corticosteroid, which requires fewer injections than treatment with most short-acting therapies, has been found to reduce inflammation and improve vision in a percentage of patients. This roundtable discussion, which took place during the 2018 annual meeting of the Vit-Buckle Society, reviews the current treatment paradigms for DME and evaluates how to customize and optimize treatment strategies geared toward individualized patient care. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:S5–S15.]

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Purpose To describe a case of acute endophthalmitis caused by Actinomyces neuii after intravitreal anti-vascular endothelial growth factor injection. Methods Observational case report, review of published literature. Results A 67-year-old white man with wet age-related macular degeneration developed endophthalmitis secondary to A. neuii on the 10th day after intravitreal anti-vascular endothelial growth factor injection. Both anterior chamber and vitreous cultures were positive for A. neuii. He was treated successfully with intravitreal injection of vancomycin and ceftazidime. Conclusion This is the first published report of culture-positive endophthalmitis caused by A. neuii after intravitreal injection.

To report a case of severe, bilateral, rapidly progressing peripheral retinal nonperfusion associated with underlying aplastic anemia.An interventional case report.A 4-year-old girl presented with decreased visual acuity. On clinical examination, she was found to have a RAPD, elevated intraocular pressure, 360° rubeosis, vitreous hemorrhage, severe exudative retinal detachment, and telangiectasia with severe peripheral retinal nonperfusion. Laboratory workup was significant for pancytopenia, and a bone marrow biopsy showed extreme hypocellularity with no malignant cells. The patient was diagnosed with primary aplastic anemia. She developed dramatic progression of retinal nonperfusion in the left eye, as well as in the fellow right eye. This bilateral retinopathy was poorly responsive to aggressive management, which included laser photocoagulation and intravitreal injections of anti-vascular endothelial growth factor medications.Asymmetric, bilateral quickly progressing peripheral retinal ischemia, in conjunction with pancytopenia and otherwise negative workup may be related to underlying bone marrow failure and aplastic anemia.

Nectin-1 is an adherens junction protein that serves as an entry receptor for neurotropic herpes simplex virus (HSV). The expression of nectin-1 in the central nervous system (CNS) has not been well defined. Furthermore, it is not known whether HSV infection has an effect on nectin-1 expression in the brain. To better understand nectin-1 expression in normal and HSV-infected brain, the authors used immunohistochemistry to characterize the expression of nectin-1 in brain tissue of uninfected adult mice and mice infected with HSV-1. In the CNS of untreated and mock-infected mice, virtually all neurons, ependymal cells, choroid plexus epithelial cells, meningothelial cells, and vascular endothelial cells expressed nectin-1. Many oligodendrocytes, astrocytes, and vascular smooth muscle cells also demonstrated nectin-1 expression, but a minority of these cells did not stain for nectin-1. Brain tissue derived from mice euthanized 5 to 8 days after intracerebral inoculation of HSV-1 showed inflammation and widespread expression of HSV-1 proteins in neurons. In HSV-1-infected brains, many inflammatory cells showed nectin-1 expression and neuronal nectin-1 staining showed a wider variation in signal strength than that detected in uninfected tissues. Many neurons showing nuclear fragmentation consistent with the morphologic appearance of apoptosis showed little or no evidence of nectin-1 expression, whereas occasional neurons stained more intensely positive for nectin-1 than those in uninfected brain tissue. These findings confirm and extend previous observations of nectin-1 expression in the nervous system and suggest that HSV-1 infection leads to changes in nectin-1 expression in the CNS, which may contribute to HSV-induced pathology and dissemination.

Nectin-1 belongs to the immunoglobulin superfamily, mediates cell-cell adhesion in cadherin-based adherens junctions, and acts as a receptor for herpes simplex virus (HSV). The goals of this study were (1) to determine whether nectin-1 is expressed in ocular tissue that is an important target of HSV infections and (2) to determine whether HSV type 1 (HSV-1) infection affects nectin-1 expression in the eye.Expression of nectin-1 and HSV-1 protein was determined by immunohistochemical analysis of ocular tissues of untreated BALB/c mice and mice that were euthanized either 7 days or 7 months after corneal inoculation of HSV-1 or sterile tissue-culture medium (mock).In ocular tissues derived from untreated and mock-infected mice, widespread nectin-1 expression was detected among cells of the corneal epithelium and endothelium, conjunctiva, lens epithelium, ciliary body, iris, choroid, and retina. However, fibroblasts in the corneal stroma and the sclera did not express detectable levels of nectin-1. Ocular tissues from mice euthanized 7 days after corneal inoculation of HSV-1 frequently demonstrated corneal ulceration and inflammation and HSV-1 protein expression in the corneal epithelium, stroma, endothelium, conjunctiva, iris, and ciliary body but rarely in the retina. Ocular tissues from mice euthanized 7 months after HSV-1 inoculation demonstrated corneal epithelial and stromal inflammation, but HSV-1 protein expression was not detected. HSV-1 infection did not lead to a loss of nectin-1 expression in any of the tissues examined. In contrast to uninfected corneas, the inflamed and vascularized stroma of infected corneas contained mononuclear inflammatory cells, vascular cells, and fibroblasts that stained positive for nectin-1.Findings report that nectin-1 is widely expressed in murine ocular tissues. Only fibroblasts in the corneal stroma and sclera of uninfected tissues were devoid of nectin-1 expression. HSV-1-infected inflamed corneas contained some stromal fibroblasts with detectable nectin-1 expression, which potentially could be targeted by the virus. Widespread nectin-1 expression in the eye suggests that this receptor may play a role in the pathogenesis of ocular HSV infections.

The development of new, abnormal and leaky blood vessels, termed choroidal neovascularization, causes loss of vision and quality of life as a result of many ocular diseases. A current therapy for a leading cause of irreversible blindness in older people in the United States, age-related macular degeneration, is intravitreal injection of ranibizumab. However, ranibizumab has also been used off-label to successfully treat a number of other ocular diseases causing significant ocular morbidity, including retinal vascular occlusion and diabetic macular edema. Despite its efficacy, the association of detectable serum levels of ranibizumab and arterial thromboembolic events in major follow-up studies since its approval by the United States Food and Drug Administration as well as its high cost relative to the possible existence of cheaper, equally efficacious alternatives has underscored the importance of understanding the mode of action and clinical utility of this novel pharmacotherapy.