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.

Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration.

PURPOSE: To describe retinal arterial occlusion and vasculitis following intravitreal brolucizumab administration in a patient with neovascular age-related macular degeneration (nAMD). OBSERVATION: An 88-year-old Caucasian woman with neovascular age-related macular degeneration (nAMD) complained of painless loss of vision with light sensitivity in both eyes (OU) four weeks after bilateral intravitreal brolucizumab. Upon examination, her visual acuity decreased to 20/40 in the right eye (OD) and 20/50 in the left eye (OS). Examination revealed 0.5+ and 1+ anterior chamber cells in OD and OS, respectively. The patient was treated with 1% prednisolone acetate eyedrops in both eyes, and after several weeks, the anterior chamber cells resolved. However, the patient still reported a decline in visual acuity (VA). Fluorescein angiography (FA) revealed retinal arterial occlusion, vasculitis, and optic nerve inflammation in the left eye. Retinal intra-arterial grayish materials were also detected. Laboratory evaluations were performed for common infectious and inflammatory causes and were normal or negative. A delayed inflammatory reaction to brolucizumab was suspected as the cause of the ocular inflammation and retinal vasculitis. An intravitreal dexamethasone implant was inserted into the left eye to treat the inflammation. One week after the dexamethasone implant, VA improved to 20/40 in OU; FA showed improvement, but residual peri-vascular leakage remained. CONCLUSION: Medication-associated uveitis is a rare adverse effect that can lead to vision loss. The index report illustrates a case of intraocular inflammation, retinal arterial vaso-occlusion and vasculitis associated with intravitreal brolucizumab. The delay in developing uveitis suggests that the inflammation is due to a delayed hypersensitivity reaction which can occur several days or weeks after administration of the inciting agent. Recently, several cases of uveitis and vasculitis associated with brolucizumab have been presented and those cases have similar features compared to the index case (1). Therapy with steroids (either intraocular or systemic), after infectious etiologies have been excluded, may be beneficial in halting inflammation and preventing further vision loss.

DIDANOSINE RETINAL TOXICITY.

PURPOSE: To report nine new cases of retinal degeneration secondary to didanosine toxicity and to summarize the previously reported cases in the literature. METHODS: This was a multicenter, retrospective, observational case study from seven institutions. Medical records of patients who demonstrated well-demarcated severe midperipheral chorioretinal degeneration and who were previously treated with didanosine therapy were collected and the following information was reviewed: age, gender, medical history, detailed medication history including current and previous antiretroviral use, ocular and retinal examination findings, and multimodal imaging findings with optical coherence tomography, fundus photography, wide-field fundus autofluorescence, and wide-field fluorescein angiography. When available, findings with electrophysiology testing and automated perimetry were also collected and reviewed. A literature review was also performed to collect all reported cases of chorioretinal degeneration secondary to didanosine toxicity. RESULTS: Nine patients were identified who had findings consistent with peripheral retinal toxicity secondary to didanosine use. Eight of the 9 patients were men, and the median age was 54 years at the time of presentation (mean: 55 years, range, 42-71 years). Snellen distance acuity ranged from 20/20 to 20/32. At least three of the cases in the series demonstrated progression of the peripheral retinal pigment epithelium and photoreceptor atrophy despite didanosine cessation. A review of the literature revealed 10 additional cases of didanosine toxicity. Seven of the 10 cases were in men (70%), and the average age was 26 years with a wide range (2-54 years). Chorioretinal findings were very similar to this cohort. CONCLUSION: Herein, we report the largest series of nine cases of peripheral chorioretinal degeneration secondary to didanosine toxicity in adults. When combined with the cases in the literature, 19 cases of didanosine toxicity, 4 of which occurred in children, were collected and analyzed. Three of the new cases presented showed clear progression of degeneration despite didanosine cessation. Newer nucleoside reverse transcriptase inhibitors may potentiate mitochondrial DNA damage and lead to continued chorioretinal degeneration.

FANCONI ANEMIA PRESENTING AS BILATERAL DIFFUSE RETINAL OCCLUSIVE VASCULOPATHY.

PURPOSE: To describe the ocular findings and subsequent workup of a 21-year-old woman with previously undiagnosed Fanconi anemia. METHODS: Observational case report and literature review. RESULTS: A 21-year-old healthy woman presented with bilateral retinal hemorrhages, telangiectasia, and severe ischemia with vascular leak. Systemic workup revealed anemia and thrombocytopenia. A diepoxybutane chromosomal breakage test confirmed the diagnosis of Fanconi anemia. CONCLUSION: Ocular complications are common in patients with Fanconi anemia and may be the presenting manifestation of the disease.

Rhegmatogenous Retinal Detachment in Patients with Acute Syphilitic Panuveitis.

PURPOSE: To describe the clinical characteristics and surgical management of rhegmatogenous retinal detachment (RD) in patients with acute syphilitic panuveitis. METHODS: Retrospective case series and comprehensive literature review. RESULTS: Including present and previously reported cases, we identified 11 eyes in 8 patients with acute syphilitic panuveitis that developed a rhegmatogenous RD. Seven of 11 eyes (63.6%) were repaired with a combined scleral buckling, vitrectomy, and endolaser photocoagulation surgery; 1 eye (9.1%) was repaired with scleral buckling only; and 2 eyes (18.2%) with vitrectomy only. Cryotherapy was used to treat a giant retinal tear in 1 eye (9.1%). Four eyes (36.4%) redetached and 3 underwent a second vitrectomy surgery. CONCLUSIONS: Although uncommon, rhegmatogenous RD can occur in patients with moderate to severe acute syphilitic panuveitis. We believe scleral buckling, vitrectomy, endolaser photocoagulation, and silicone oil tamponade give the best chance for successful retinal reattachment.

SUSAC SYNDROME.

PURPOSE: To describe an atypical presentation of Susac syndrome. METHODS: Observational case report. RESULTS: A 44-year-old man with no significant medical history presented with inferonasal visual field loss in his left eye of several months of duration. He was found to have bilateral migratory arteritis with focal areas of arteriolar occlusion in both eyes and peripheral ischemia superotemporally in his left eye. An extensive hematologic workup was negative for autoimmune disease or coagulopathy. Magnetic resonance imaging with contrast of his brain revealed a hyperintense lesion in the splenium of the corpus callosum. Auditory testing was significant for nonspecific high-frequency hearing loss in the right ear. Given the full clinical picture, a diagnosis of Susac syndrome was made. CONCLUSION: Susac syndrome is a multisystemic, immune-mediated occlusive endotheliopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. However, patients may present with varying degrees of this triad; thus, there should be a high index of suspicion in patients presenting with multiple artery occlusions or multifocal arteritis.

Spectral domain optical coherence tomography findings in eyes with acute ischaemic retinal whitening.

Acute retinal ischaemia presents in various forms depending on the type and location of the associated vascular occlusion. Cotton wool spots have been considered one manifestation of ischaemia and represent swelling in the nerve fibre layer. However, clinical retinal whitening also occurs in areas not affected by cotton wool spots, and has distinguishing spectral domain optical coherence tomography (SD-OCT) features. We present SD-OCT findings of hyper-reflectivity and thickening in four eyes with representative retinal arterial or retinal venous occlusions, specifically branch retinal artery occlusion, central retinal vein occlusion, Purtscher-like retinopathy and ophthalmic artery occlusion. The spectrum of retinal ischaemia from various causes was found to manifest in inner nuclear layer hyper-reflectivity and thickening on SD-OCT. En Face OCT imaging further characterises the topographical distribution of ischaemia, and reveals patterns which provide insight into the pathological processes involved.

Central serous chorioretinopathy after trabeculectomy in a patient with microphthalmos and congenital rubella syndrome.

PURPOSE: To describe a case of central serous chorioretinopathy after trabeculectomy surgery in an eye with microphthalmos in the setting of congenital rubella syndrome. METHODS: A Case report with color fundus photographs, fluorescein angiography, and spectral domain optical coherence tomography. RESULTS: A 46-year-old African American man, with a history of congenital heart disease and bilateral hearing loss, developed persistent vision loss in the left eye after trabeculectomy surgery. Ocular examination revealed bilateral salt-and-pepper retinopathy and a serous detachment in the macula of the left eye. Fluorescein angiography showed an early "smoke-stack" pattern of hyperfluorescence with progressive filling of the subretinal space consistent with central serous chorioretinopathy. Spectral domain optical coherence tomography documented both size and extent of the serous retinal detachment and showed several pigment epithelial detachments. B-scan ultrasonography confirmed the serous retinal detachment on the left but showed no evidence of posterior eye wall thickening or of retrobulbar fluid. An A-scan revealed an axial length of 21.8 mm on the right and 19.7 mm on left eye, confirming microphthalmos and supporting the suspected diagnosis of congenital rubella syndrome. CONCLUSION: Although uncommon, central serous chorioretinopathy can occur in anatomically small eyes after trabeculectomy surgery.

Clinical presentation of chorioretinitis sclopetaria.

PURPOSE: To report the clinical manifestations of a case of chorioretinitis sclopetaria. METHODS: Observational case report. RESULTS: A 30-year-old prison inmate sustained a traumatic injury to his left eye. Fundus examination showed a large chorioretinal detachment revealing bare sclera, vitreous hemorrhage, and commotio retinae. CONCLUSION: The patient was diagnosed with chorioretinitis sclopetaria. Given the mechanism of injury, retinal detachment is rare. Observation is appropriate as initial management.

Acute retinal necrosis secondary to multidrug-resistant herpes simplex virus 2 in an immunocompetent adolescent.

PURPOSE: To report the clinical course of a patient with acute retinal necrosis resulting from a multidrug-resistant strain of herpes simplex virus 2. METHODS: Observational case report. RESULTS: A 17-year-old man with no identifiable immune deficiency presented with pain and decreased vision in his left eye. He had dense anterior and posterior segment inflammation with retinal whitening suggestive of acute retinal necrosis, which progressed despite treatment with intravenous acyclovir, methylprednisolone, and ganciclovir. A transition to intravitreal and intravenous foscarnet led to clinical improvement. Genetic analysis revealed the etiology to be a multidrug-resistant strain of herpes simplex virus 2. CONCLUSION: Antiviral resistance is an uncommon finding among viruses causing acute retinal necrosis in immunocompetent patients. Patients with these infections may be adequately treated with prompt recognition and a change in therapy to alternative antiviral agents such as foscarnet.

En face spectral domain optical coherence tomography analysis of lamellar macular holes.

PURPOSE: To analyze the anatomical characteristics of lamellar macular holes using cross-sectional and en face spectral domain optical coherence tomography. METHODS: Forty-two lamellar macular holes were retrospectively identified for analysis. The location, cross-sectional length, and area of lamellar holes were measured using B-scans and en face imaging. The presence of photoreceptor inner segment/outer segment disruption and the presence or absence of epiretinal membrane formation were recorded. RESULTS: Forty-two lamellar macular holes were identified. Intraretinal splitting occurred within the outer plexiform layer in 97.6% of eyes. The area of intraretinal splitting in lamellar holes did not correlate with visual acuity. Eyes with inner segment/outer segment disruption had significantly worse mean logMAR visual acuity (0.363 ± 0.169; Snellen = 20/46) than in eyes without inner segment/outer segment disruption (0.203 ± 0.124; Snellen = 20/32) (analysis of variance, P = 0.004). Epiretinal membrane was present in 34 of 42 eyes (81.0%). CONCLUSION: En face imaging allowed for consistent detection and quantification of intraretinal splitting within the outer plexiform layer in patients with lamellar macular holes, supporting the notion that an area of anatomical weakness exists within Henle's fiber layer, presumably at the synaptic connection of these fibers within the outer plexiform layer. However, the en face area of intraretinal splitting did not correlate with visual acuity, disruption of the inner segment/outer segment junction was associated with significantly worse visual acuity in patients with lamellar macular holes.

A national survey of practice patterns: temporal artery biopsy.

OBJECTIVE: To assess current clinical practice patterns for temporal artery biopsy (TAB) among clinicians in establishing the diagnosis of giant cell arteritis. DESIGN: A survey was sent via e-mail using the Survey Monkey website (www.surveymonkey.com; accessed January 24, 2013). The survey initially was sent in July 2010 and continued through October 2010. PARTICIPANTS: The survey was sent via e-mail to the members and affiliates of the American Society of Ophthalmic Plastic and Reconstructive Surgery, the North American Neuro-Ophthalmology Society, and the American College of Rheumatology. METHODS: Data from the survey were collected via Survey Monkey and data analysis was performed using the Fisher exact test and Wilcoxon rank-sum test. MAIN OUTCOME MEASURES: Response to the survey questions on primary unilateral versus bilateral biopsy, performing second-side biopsy if first side results were negative, and the duration for which biopsy findings are reliable after initiating immunosuppressive therapy. RESULTS: The self-described primary subspecialty of the 1074 respondents was as follows: oculoplastic surgery (n = 127), neuro-ophthalmology (n = 119), rheumatology (n = 799), and other (n = 28). Overall, 66% of respondents advocated initial unilateral TAB, 18% advocated bilateral biopsy in all cases, and 16% recommended either unilateral or bilateral TAB depending on the degree of clinical suspicion. Rheumatologists were 4.5 times more likely to advocate initial bilateral biopsy than neuro-ophthalmologists or oculoplastic surgeons (P<0.0001, Fisher exact test). Most respondents believed that biopsy results were accurate for more than 14 days. These results were not affected by stratification of years in practice by the Kruskal-Wallis rank-sum test. CONCLUSIONS: Temporal artery biopsy practices vary greatly among treating physicians. This lack of consensus underscores the need for a systematic assessment of varying practice patterns. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk factors for retinal detachment following cataract surgery.

PURPOSE OF REVIEW: To review and evaluate the current literature on the incidence and risk factors for rhegmatogenous retinal detachment (RRD) following cataract surgery. RECENT FINDINGS: RRD is a serious complication of cataract surgery that can occur in the early or late postoperative periods. Identifying factors that increase the risk of pseudophakic retinal detachment can aid in management. Recent studies support long established risk factors for retinal detachment including intraoperative complications such as posterior capsular rupture (PCR). In addition, the current literature further defines the risk for pseudophakic retinal detachment associated with younger age at time of surgery, high myopia, and male sex in several large retrospective studies. Two recent articles also examine the state of the vitreous before and after cataract surgery and find that patients are more likely to develop posterior vitreous detachment postoperatively, possibly contributing to the increased risk of RRD. SUMMARY: Younger age, high myopia, and male sex continue to be associated with higher risk of pseudophakic retinal detachment. Intraoperative complications such as PCR also increase the retinal detachment risk. Given the high volume of cataract surgeries performed each year, pseudophakic retinal detachment contributes significantly to visual morbidity in the United States and Europe.

Ischemia-reperfusion impairs ascending vasodilation in feed arteries of hamster skeletal muscle.

OBJECTIVE: Vasodilation originating within the microcirculation ascends into proximal feed arteries during muscle contraction to attain peak levels of muscle blood flow. Ascending vasodilation (AVD) requires an intact endothelium, as does conducted vasodilation in response to acetylcholine (ACh). Whereas ischemia-reperfusion (I-R) can affect endothelial cell function, the effect of I-R on AVD is unknown. The authors tested the hypothesis that I-R (1h-1h) would impair AVD. METHODS: Using the retractor muscle of anesthetized hamsters, contractions were evoked using field stimulation (200 ms at 40 Hz every 2 s for 1 min) and ACh was delivered using microiontophoresis (1 microm tip, 500-4000 ms pulse at 800 nA). Feed artery responses were monitored 500-1500 microm upstream. RESULTS: Neither resting (51 +/- 4 microm) nor maximal diameter (81 +/- 5 microm; 10 microm sodium nitroprusside) following I-R (n = 8) were different from time-matched controls (n = 10). With peak active tension of 23 +/- 4 mN x mm(-2), control AVD was 26 +/- 2 microm. Following I-R, active tension fell by 48% (p < .05) and AVD by 57% (p < .05). Stimulation at 70 Hz restored active tension but AVD remained depressed by nearly half (p < .05), as did local and conducted responses to ACh. Nevertheless, control responses to 500 ms ACh were restored by increasing stimulus duration to 4000 ms. CONCLUSIONS: Ischemia-reperfusion impairs the initiation of feed artery dilation with muscle contraction and with ACh while conduction along the vessel wall is preserved. Respective components of endothelial cell signaling events may differ in their susceptibility to I-R.

Sympathetic neural inhibition of conducted vasodilatation along hamster feed arteries: complementary effects of alpha1- and alpha2-adrenoreceptor activation.

Vasodilatation initiated on arterioles of skeletal muscle ascends into the proximal feed arteries through cell-to-cell conduction along the endothelium and into smooth muscle. Whereas perivascular sympathetic nerve activity (SNA) can inhibit conducted vasodilatation and restrict muscle blood flow, the signalling events mediating this interaction are poorly defined. Therefore, using isolated pressurized (75 mmHg) feed arteries (diameter (microm) at rest = 53 +/- 3; maximum = 99 +/- 2; n = 86) of the hamster retractor muscle, we tested the hypothesis that distinct yet complementary signalling pathways underlie the ability of SNA to inhibit conduction. Conducted vasodilatation was initiated using ACh microiontophoresis (1 microA; 250, 500 and 1000 ms) and SNA was initiated using local field stimulation (30-50 V; 1 ms at 2, 8 and 16 Hz). With vasodilatations of 5-20 microM, conduction increased with ACh pulse duration and was inhibited progressively as the frequency of SNA increased. During SNA, conduction was partially restored with inhibition of alpha1- (0.1 microM prazosin) or alpha2- (0.1 microM RX821002) adrenoreceptors and fully restored with both antagonists present. Activating alpha1- (50 nM phenylephrine) or alpha2- (1 microM UK 14,304) adrenoreceptors inhibited conduction partially and their simultaneous activation inhibited conduction cumulatively (P < 0.05). Elevated [K+]o (30 or 40 mM) or phorbol esters (0.5 microM) also inhibited conduction yet similar constriction with l-NNA (50 microM) or Bay K 8644 (10 nM) did not. Thus, the activation of alpha1- and alpha2-adrenoreceptors inhibits conducted vasodilatation through complementary signalling events. With robust coupling along the endothelium, our modelling predicts that the inhibition of conduction by SNA can be explained by reduced electrical coupling through myoendothelial gap junctions or greater current leak across smooth muscle cell membranes.

Independence of connexin expression and vasomotor conduction from sympathetic innervation in hamster feed arteries.

OBJECTIVE: Vasomotor responses can travel along the wall of resistance microvessels by two distinct mechanisms: cell-to-cell conduction through gap junctions or the release of neurotransmitter along perivascular nerves. It is unknown whether vascular innervation influences the expression of connexin molecules which comprise gap junctions, or the conduction of vasomotor responses. In feed arteries of the hamster retractor muscle (RFA), the authors tested whether sympathetic denervation would alter the expression of connexin isoforms and the conduction of vasomotor responses. METHODS: Using intact vessels with sympathetic innervation and those 7-8 days following denervation surgery, mRNA expression was quantified using real-time PCR, cellular localization of Cx protein was characterized using immunohistochemistry, and vasomotor responses to dilator and constrictor stimuli were evaluated in isolated pressurized RFA. RESULTS: Connexin protein localization and mRNA expression were similar between innervated and denervated vessels. mRNA levels were Cx43 = Cx37 > Cx45 >> Cx40. Vasodilation to acetylcholine conducted >/=2000 microm along innervated and denervated vessels, as did the biphasic conduction of vasoconstriction and vasodilation in response to KCl. Vasoconstriction to phenylephrine conducted <500 microm and was attenuated (p <.05) in denervated vessels. CONCLUSIONS: The profile of connexin expression and the conduction of vasomotor responses are largely independent of sympathetic innervation in feed arteries of the hamster retractor muscle (RFA).

Sympathetic nerves inhibit conducted vasodilatation along feed arteries during passive stretch of hamster skeletal muscle.

Ascending vasodilatation is integral to blood flow control in exercising skeletal muscle and is attributable to conduction from intramuscular arterioles into proximal feed arteries. Passive stretch of skeletal muscle can impair muscle blood flow but the mechanism is not well understood. We hypothesized that the conduction of vasodilatation along feed arteries can be modulated by changes in muscle length. In anaesthetized hamsters, acetylcholine (ACh) microiontophoresis triggered conducted vasodilatation along feed arteries (diameter, 50-70 microm) of the retractor muscle secured at 100 % resting length or stretched by 30 %. At 100 % length, ACh evoked local dilatation (> 30 microm) and this response conducted rapidly along the feed artery (14 +/- 1 microm dilatation at 1600 microm upstream). During muscle stretch, feed arteries constricted approximately 10 microm (P < 0.05) and local vasodilatation to ACh was maintained while conducted vasodilatation was reduced by half (P < 0.01). Resting diameter and conduction recovered upon restoring 100 % length. Sympathetic nerve stimulation (4-8 Hz) produced vasoconstriction and attenuated conduction in the manner observed during muscle stretch, as did noradrenaline or phenylephrine (10 nM). Inhibiting nitric oxide production (Nomega-nitro-L-arginine, 50 microM) produced similar vasoconstriction yet had no effect on conduction. Phentolamine, prazosin, or tetrodotoxin (1 microM) during muscle stretch abolished vasoconstriction and restored conduction. Inactivation of sensory nerves with capsaicin had no effect on vasomotor responses. Thus, muscle stretch can attenuate conducted vasodilatation by activating alpha-adrenoreceptors on feed arteries through noradrenaline released from perivascular sympathetic nerves. This autonomic feedback mechanism can restrict muscle blood flow during passive stretch.