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Background: This pilot study aimed to evaluate the Retinal Function Imager (RFI) for visualizing retinal vasculature and assessment of blood flow characteristics in patients with retinal vasculitis. The RFI is a non-invasive imaging device measuring the blood flow velocity (BFV) in secondary and tertiary retinal vessels using hemoglobin as an intrinsic motion-contrast agent. Methods: To test the feasibility of the RFI for patients with retinal vasculitis, capillary perfusion maps (nCPMs) were generated from 15 eyes of eight patients (five females; mean age: 49 ± 12 years) with a mean uveitis duration of 74 ± 85 months. Five of these patients had birdshot chorioretinopathy, and three had primarily non-occlusive venous retinal vasculitis of unknown origin. To reflect that the BFV may be more reduced in patients with prolonged disease, patients were classified into a short-term (uveitis duration: 8-15 months) and a long-term uveitis group (uveitis duration: 60-264 months). Data were compared with healthy controls (16 eyes of 11 patients; mean age 45 ± 12 years; 8 females). Results: The mean BFV in the controls was 3.79 ± 0.50 mm/s in the retinal arteries and 2.35 ± 0.44 mm/s in the retinal veins, which was significantly higher compared to the retinal vasculitis group. Patients revealed an arterial BFV of 2.75 ± 0.74 mm/s (p < 0.001) and a venous BFV of 1.75 ± 0.51 mm/s (p = 0.016). In the short-term group, a trend towards a decreased venular and arteriolar BFV was seen, while a significant reduction was observed in the long-term group. The patients' microvasculature anatomy revealed by the nCPMs appeared unevenly distributed and a lower number of blood vessels were seen, along with a lower degree of complexity of their branching patterns, when compared with controls. Conclusions: This study demonstrated a reduction in venular and arteriolar BFVs in patients with retinal vasculitis. BFV alterations were already observed in early disease stages and became more pronounced in progressed disease. Additionally, we showed that retinal microvasculature changes may be observed by nCPMs. Retinal imaging with the RFI may serve as a diagnostic and quantifying tool in retinal vasculitis.
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PURPOSE: To assess the validity of retinal vasculitis as the preferred diagnostic term for multiple conditions. DESIGN: Perspective. METHODS: This Perspective is based on expert opinion and review of literature focused on the current nosology and pathology of retinal vasculitis. Interpretation of the subset of intraocular inflammation named "retinal vasculitis" based on fundamental knowledge of the blood-retinal barrier, the neurovascular unit, and pathological and functional responses to a variety of stimuli is provided. Correlation with multimodal imaging and known mechanisms of immunologically mediated disease are discussed. RESULTS: A search of Medline in early 2024 for the phrase "retinal vasculitis" resulted in 2041 citations encompassing immunologic, genetic, neoplastic, infectious, drug-related, and ischemia-related disorders. Classification schemes and angiographic grading systems are descriptive and do not address pathologic mechanisms adequately, in part due to lack of histologic confirmation. Although optical coherence tomography (OCT) angiography holds promise for better imaging of retinal vascular changes, it does not reveal the key feature of leakage and only partially improves understanding of pathophysiology. Diagnosing catastrophic retinal vascular occlusion after intravitreal injections as a retinal vasculitis is the most recent example of speculative application of the term to complex and rare disorders. CONCLUSIONS: Retinal vasculitis is a diagnostic term that is over-used and imprecise. Revised nosology should limit the term to primary inflammation of the retinal vasculature itself that results in opening of the blood-retinal barrier with or without retinal vascular occlusions. Pending new histologic or mechanistic evidence, the provisional term of "retinal vascular inflammation" or "retinal vasculopathy" should be used for leakage or occlusion occurring in the context of intraocular inflammation.
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Purpose: To describe a patient with retinal vasculitis after a single intravitreal injection (IVI) of pegcetacoplan. Methods: A case and its findings were analyzed. Results: An 80-year-old woman was treated with pegcetacoplan for subfoveal geographic atrophy. Ten days later, the patient noted "purple iridescent waves" but did not immediately report it. On day 18, she presented with pain and decreased visual acuity from 20/80 (pinhole) preinjection to 20/150 postinjection. No signs of inflammation were observed, and she was treated for high intraocular pressure (30 mm Hg). On day 23, iritis was noted. The fluorescein angiogram showed severe occlusive vasculitis involving all quadrants and the macula. The vasculitis/neuroretinitis laboratory panels were negative, and no contributing systemic features were identified other than well-controlled diabetes. Conclusions: In this patient, occlusive retinal vasculitis occurred shortly after a single IVI of pegcetacoplan.
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Purpose: To analyze post-marketing cases of retinal vasculitis after intravitreal pegcetacoplan. Methods: The American Society of Retina Specialists (ASRS) Research and Safety in Therapeutics (ReST) Committee as well as an expert panel performed a retrospective review of cases of retinal vasculitis reported to the ASRS. Clinical and imaging characteristics were reviewed for evidence of retinal vasculitis and analyzed. Results: Fourteen eyes of 13 patients were confirmed to have retinal vasculitis by review of imaging studies. All cases occurred after the first pegcetacoplan injection. Occlusive retinal vasculopathy was confirmed in 11 eyes (79%). Patients presented a median of 10.5 days (range, 8-23 days) after pegcetacoplan injection. All eyes had anterior chamber inflammation, and 12 eyes (86%) had vitritis. Vasculopathy involved retinal veins (100%) more than arteries (73%), and 12 eyes (86%) had retinal hemorrhages. The median visual acuity (VA) was 20/60 (range, 20/30-5/200) at baseline, 20/300 (range, 20/100-no light perception [NLP]) at vasculitis presentation, and 20/200 (range 20/70-NLP) at the last follow-up. Eight eyes (57%) had more than a 3-line decrease in VA, and 6 eyes (43%) had more than a 6-line decrease in VA from baseline to the final follow-up, including 2 eyes that were enucleated. Six eyes (43%) developed signs of anterior segment neovascularization. Conclusions: There is currently no known etiology for vasculitis in this series. Optimum treatment strategies remain unknown. Infectious etiologies should be considered, and corticosteroid treatments may hasten resolution of inflammatory findings. Continued treatment of affected patients with pegcetacoplan should be avoided.
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INTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts. METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey. RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors. CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.
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AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.
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Herpes Simples , Herpes Zoster Oftálmico , Herpes Zoster , Uveíte Anterior , Uveíte , Humanos , Herpesvirus Humano 3 , Simplexvirus , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/tratamento farmacológico , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Atrofia , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológicoRESUMO
AIMS: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide. METHODS: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform. RESULTS: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts). CONCLUSIONS: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.
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Infecções por Citomegalovirus , Uveíte Anterior , Humanos , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Humor Aquoso , Ganciclovir/uso terapêutico , Antivirais/uso terapêutico , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológicoRESUMO
PURPOSE: To assess longitudinal relationships among visual function and anatomical measures of gene therapy in G11778A Leber hereditary optic neuropathy (LHON). DESIGN: Phase 1 clinical trial. METHODS: This was a single-institution study of patients with G11778A LHON. Patients with chronic bilateral visual loss >12 months (group 1, n = 11), acute bilateral visual loss <12 months (group 2, n = 9), or unilateral visual loss (group 3, n = 8) were administered unilateral intravitreal AAV2(Y444,500,730F)-P1ND4v2 injection with low, medium, high, and higher doses to worse eye for groups 1 and 2 and better eye for group 3. Oucome measures were best-corrected visual acuity (BCVA), visual field mean deviation (VF MD), steady-state pattern electroretinogram (SS-PERG), optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness and ganglion cell+inner plexiform layer (GCIPL) thickness, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores. Mean follow-up was 33.6 months (range = 18-36 months). RESULTS: Baseline SS-PERG amplitude was much reduced in both eyes of all groups including asymptomatic eyes of group 3, and showed no appreciable changes irrespective of disease stage and treatment. Significant and progressive GCIPL and RNFL thinning occurred in all eyes; BCVA and VF MD fluctuated in treated and fellow eyes, with some eyes having modest improvement that may be related to natural history or to gene therapy. Mean NEI-VFQ-25 scores declined in group 3 subjects (P = .023), CONCLUSION: Asymptomatic eyes in LHON patients with unilateral visual loss may be beyond the window of effective neuroprotection given reduced GCIPL and SS-PERG. Randomization of patients to an untreated control group would help to assess treatment effect by accounting for variable natural history. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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Atrofia Óptica Hereditária de Leber , Humanos , Terapia Genética , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/terapia , Células Ganglionares da Retina/fisiologia , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/terapia , Acuidade Visual , Campos VisuaisRESUMO
Purpose: To report panuveitis with exudative retinal detachments in a healthy 27-year-old woman with biallelic mutations in the RPE65 gene, who underwent bilateral sequential gene therapy with subretinal administration of voretigene neparvovec-rzyl. Observations: Visual acuity improved for 30 days after surgery as oral corticosteroids were tapered. At postoperative week 6, vision declined due to sudden onset uveitis and exudative retinal detachments in both eyes. HLA Class II typing revealed the haplotype associated with sympathetic ophthalmia and Vogt-Koyanagi-Harada (VKH). The inflammation improved after corticosteroid, mycophenolate mofetil, and adalimumab therapy while vision remained poor. Conclusions and Importance: Surgically-induced sympathetic ophthalmia is a plausible explanation for the clinical findings; surgery of both eyes within one week would conceal the inciting eye. VKH or inflammation related to the gene therapy are other possible etiologies but severe bilateral panuveitis has not been reported with voretigene neparvovec-rzyl. Informed consent for gene therapy surgery should include a discussion of the rare complication of sympathetic ophthalmia following vitrectomy surgery.
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Purpose: Although conjunctivitis represents the most common ocular manifestation of COVID-19 infection, sight-threatening retinal involvement has been reported. Herein, we report and characterize with multimodal retinal imaging 5 cases of acute vision loss secondary to presumed chorioretinal vasculopathy temporally associated with COVID-19 infection with varying severity, visual morbidity, and treatment response, and review the available literature on the association between COVID-19 infection and retinal microvascular changes. Design: Observational case series and literature review. Methods: Multicenter case series of 5 patients who presented to academic centers and private offices with acute vision loss temporally associated with COVID-19 infection. A review of the literature was conducted using online databases. Results: 10 eyes of 5 patients, 3 men and 2 women, with a mean age of 30.8 years (median 33, range 16-44) were described. All patients had a recently preceding episode of COVID-19, with symptomatology ranging from mild infection to life-threatening encephalopathy. Treatment for their retinal disease included topical, oral, intravitreal, and intravenous steroids, steroid-sparing immunosuppression, retinal photocoagulation, antivirals, and antiplatelet and anticoagulant agents. Treatment response and visual recovery ranged from complete recovery of baseline acuity to permanent vision loss and need for chronic immunosuppression. Conclusions and Importance: Clinicians should be mindful of the potential for vision-threatening retinal involvement after COVID-19 infection. If found, treatment with both anti-inflammatory therapy and anticoagulation should be considered, in addition to close monitoring, as some patients with this spectrum of disease may require chronic immune suppression and/or anti-VEGF therapy.
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PURPOSE: Exogenous endophthalmitis (ExE) results from microbial infection as a complication of ocular surgery, penetrating ocular trauma, and intraocular foreign bodies. We herein review the classification of ExE, etiological agents, differential diagnosis and therapeutic challenges. METHODS: Narrative Literature Review. RESULTS: Identification of the causative agent through ocular fluid analysis is central in the diagnostic work-up of ExE. Prompt intravitreal antimicrobial therapy is key to successful management of ExE and vitrectomy is essential in severe cases. In culture-negative cases, and in the presence of specific features, a diagnosis of sterile intraocular inflammation or toxic syndrome should be suspected. CONCLUSION: Strict adherence to treatment guidelines may improve outcomes of ExE, however the ultimate prognosis, especially in severe cases, may depend more on the virulence of the causative organism and associated ocular complications. Accurate differential diagnosis and effective treatment are crucial elements in the management and prognosis of non-infectious masquerades of ExE.
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Endoftalmite , Corpos Estranhos no Olho , Uveíte , Humanos , Endoftalmite/tratamento farmacológico , Uveíte/tratamento farmacológico , Vitrectomia/métodos , Resultado do Tratamento , Corpos Estranhos no Olho/diagnóstico , Antibacterianos/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: An effective therapy to reduce the number and severity of HLA-B27-related acute anterior uveitis (AAU) recurrences represents a clinical need. Curcumin is a promising therapeutic option in various inflammatory eye diseases. To enhance its absorption and eye tissue selectivity, a phospholipidic-curcumin complex (PHBC) has been formulated (Iphytoone®, Eye Pharma S.p.A.). AIMS: This study investigates if PHBC is effective and safe to decrease the number and intensity of HLA-B27-related AAU relapses. METHODS: HLA-B27-related AAU patients were randomly divided to receive PHBC or placebo for 12 months (NCT03584724). RESULTS: Compared with the previous year, the number of relapses decreased in both groups. The proportion of responders was significantly higher in the PBHC group. The severity of attacks was comparable. The study drug was well tolerated. CONCLUSIONS: A beneficial effect of PHBC treatment is suggested because the proportion of responders was significantly higher in this group of patients.
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Curcumina , Uveíte Anterior , Uveíte , Humanos , Antígeno HLA-B27 , Curcumina/uso terapêutico , Uveíte/tratamento farmacológico , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Recidiva , Doença Aguda , Anti-Inflamatórios/uso terapêuticoRESUMO
PURPOSE: To report surgical observations formulated during the first 120 cases of subretinal gene therapy in patients with inherited retinal degenerations (IRDs). METHODS: A two-surgeon team compiled surgical observations and formulated surgical pearls based on the consecutive cases of subretinal viral vector injection in patients enrolled in clinical trials focusing on choroideremia, achromatopsia, and RP GTPase regulator associated retinitis pigmentosa, as well as patients with retinal pigment epithelium-specific-65-kDa (RPE65) associated Leber congenital amaurosis receiving Food and Drug Administration-approved voretigene neparvovec-rzyl therapy. RESULTS: One hundred twenty subretinal surgeries were performed by a two-surgeon team. Key anatomical features pertinent to surgical management were noted and are described in this article. Surgical decision making for successful subretinal administration of viral vectors and management of potential surgical challenges were formulated. CONCLUSION: Lessons learned during subretinal gene therapy cases may be helpful to other surgeons entering clinical trials or performing postapproval gene therapy administration. Surgical pearls outlined in this article may also be helpful for other targeted subretinal therapies, such as cellular transplantation or retinal prosthesis implantation.
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Amaurose Congênita de Leber , Degeneração Retiniana , Retinose Pigmentar , Humanos , Retina , Terapia Genética , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/terapia , Degeneração Retiniana/terapia , cis-trans-Isomerases/genéticaRESUMO
PURPOSE: This report describes a case of hereditary transthyretin amyloidosis in an 82-year-old woman who presented with bilateral retinal arteriolar vascular sheathing and vitreous hemorrhage in one eye. METHODS: The patient underwent a full history, physical examination, genetic workup, and cardiac imaging to establish the diagnosis. Fundus photographs, optical coherence tomography, fluorescein angiography, and indocyanine green angiography were performed throughout the patient's treatment course. RESULTS: Fundus examination demonstrated segmental sheathing of the retinal arterioles, telangiectasias, and intraretinal hemorrhages in both eyes without neovascularization. Fluorescein angiography revealed delayed filling of the nasal retinal arterioles in the right eye with severe temporal nonperfusion and areas hyperfluorescent segmental sheathing in both eyes. Ocular coherence tomography demonstrated retinal vessels with hyperreflective thickened walls. Cardiac amyloid nuclear scan was consistent with transthyretin-mediated amyloidosis amyloid heart disease, and genetic testing confirmed a heterozygous pathogenic transthyretin mutation: c.290 C>A (p.Ser97Tyr) also known as Ser77Tyr. CONCLUSION: Amyloidosis should be considered in the differential of vasculitis and vitreous hemorrhage with or without significant vitreous opacities. Ophthalmologists aware of this diagnosis should complete a full review of systems with specific focus on cardiac history and symptoms of peripheral neuropathy when amyloidosis is in the differential.
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Neuropatias Amiloides Familiares , Oftalmopatias , Doenças Retinianas , Feminino , Humanos , Idoso de 80 Anos ou mais , Hemorragia Vítrea , Pré-Albumina/genética , Doenças Retinianas/diagnóstico , Oftalmopatias/diagnóstico , Angiofluoresceinografia , Tomografia de Coerência ÓpticaRESUMO
Purpose: Ophthalmia nodosa (ON) is a rare but important disease describing ocular inflammation caused by injury from insect hairs ("setae"). Type V ON occurs when there is vitreoretinal involvement. Treatment with systemic steroids are first-line, but vitrectomy is indicated in resistant cases. The purpose of this study was to illustrate how multimodal imaging can facilitate diagnosis and management of ON. Observations: This is a single retrospective case report of a patient who presented to Bascom Palmer Eye Institute with Type V ON. Multimodal imaging in a patient with Type V ON was illustrated. A moth seta was localized to the anterior vitreous cavity. Intraocular inflammation responded to 2 weeks of high-dose oral prednisone. Conclusions and Importance: Multimodal imaging may guide diagnosis and management of ON by documenting baseline features of ON and facilitating comparison at follow up visits. This allows for safe non-surgical management of Type V ON. Long-term follow up would be necessary to determine whether subsequent surgical intervention was needed in this case.
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INTRODUCTION: Vitreoretinal lymphoma is a rare ocular cancer with high morbidity and mortality despite treatment. Diagnosis by cytopathology is often delayed, and various molecular and image-based investigations have been developed. Diverse treatments are used, but there is a limited medical evidence to differentiate their effectiveness. We designed an international registry that would collect diagnostic, treatment and outcomes data, to establish new evidence for the management of this cancer. METHODS AND ANALYSIS: The International Vitreoretinal B-Cell Lymphoma Registry will accrue data retrospectively for individuals aged 18 years or older, diagnosed with new or recurrent vitreoretinal B-cell lymphoma on or after 1 January 2020. A steering committee of subspecialised ophthalmologists identified 20 key clinical data items that describe patient demographics, tissue involvements, diagnostic testing, ocular and systemic treatments and treatment complications, and visual acuity and survival outcomes. Customised software was designed to permit collection of these data across a single baseline and multiple follow-up forms. The platform collects data without identifiers and at 3 month reporting intervals. Outcomes of the project will include: (1) descriptions of clinical presentations, and diagnostic and therapeutic preferences; (2) associations between clinical presentations, and diagnostics and treatments, and between diagnostics and treatments (assessed by ORs with 95% CIs); and (3) estimations of rates of vision loss, and progression-free and overall survival (assessed by Kaplan-Meier estimates). ETHICS AND DISSEMINATION: The registry has received Australia-wide approval by a national human research ethics committee. Sites located outside Australia are required to seek local human research ethics review. Results generated through the registry will be disseminated primarily by peer-reviewed publications that are expected to inform clinical practice, as well as educational materials.