Use of immunomodulators in non-infectious uveitis: lights and shadows.

Non-infectious uveitis (NIU) is one of the leading causes of sight impairment worldwide. Corticosteroids are the mainstay treatment for acute NIU, although their known systemic and ocular side effects limit their long-term use. The most common types of immunosuppressants used as steroid-sparing treatment are non-biologic drugs, particularly antimetabolites (methotrexate, mycophenolate mofetil, and azathioprine) and biologic drugs, mainly TNF-α inhibitors such as Adalimumab or Infliximab. Antimetabolites have shown their effectiveness in the treatment of NIU in individual and comparative studies, being methotrexate and mycophenolate mofetil usually preferred over azathioprine. The choice of which antimetabolite to use at first is not well defined, and decisions usually depend on the patient's characteristics and the physician's preferences. Treatment of NIU with biologic drugs, and particularly TNF-α inhibitors, has significantly increased in the last years and is considered an important alternative in patients not responding to first-line immunomodulators such as antimetabolites. However, data regarding how different immunomodulators or biologic drugs perform in different NIU is still limited, and little is known about the optimization of both biologic and non-biologic drugs when used in NIU. Further randomized clinical trials and comparative studies are required to achieve more understanding and better results when addressing complicated NIU. The purpose of this review is to provide a comprehensive overview of the use of non-biologic and biologic drugs in NIU, which may be useful for clinicians in their daily practice, and to address those aspects that are less known about these treatments as well as their weaknesses.

Choroidal involvement in acute retinal necrosis: case series and review of the literature.

PURPOSE: To show the role of multimodal imaging in identifying choroidal involvement in acute retinal necrosis (ARN). METHODS: Retrospective case series of ARN patients. Clinical data, including medical history, clinical features and multimodal imaging findings, were collected. RESULTS: Three patients were included. Imaging modalities, such as indocyanine green angiography and optical coherence tomography, were critical in showing choroidal involvement in ARN. CONCLUSION: Choroidal involvement may occur in ARN along with the well-known retinal features.

Real-World Experience of Fluocinolone Acetonide 0.19 mg in the Management of Non-Infectious Uveitis.

PURPOSE: This study aims to evaluate the real-world efficacy and safety profile of fluocinolone acetonide (FAc) implants for the treatment of non-infectious uveitis (NIU). METHODS: A retrospective, observational study was conducted at Moorfields Eye Hospital, London, involving patients who received FAc 0.19 mg implants (Iluvien®) for NIU. 2-year follow-up data on baseline characteristics, indications, and outcomes was collected. The primary indicator for treatment failure was defined as the need for rescue treatment with dexamethasone (DEX) implants, while secondary indicators included changes in steroid and systemic immunosuppression requirements, or the need for a second FAc implant before 3 years. The occurrence of complications was collected. RESULTS: Of the 146 eyes treated with FAc implants, 24.0% experienced treatment failure requiring DEX implant within 2 years. About 42.9% required this within the first 6 months. There was an increase in the number of patients requiring steroids and/or systemic immunosuppression. Within the first 2 years post-FAc implant, only 13.7% experienced an IOP rise, with 4.1% requiring IOP-lowering surgery. About 57.9% of the phakic eyes developed cataracts. CONCLUSION: This study provides valuable real-world evidence supporting the efficacy of FAc implant in NIU. It demonstrates a good safety profile at 2 years, with a significant reduction in uveitis recurrence rate and treatment burden. Our results are especially pertinent to the treatment of uveitic cystoid macular oedema (CMO), which was the primary indication in over 75% of our patients. Furthermore, it suggests that while FAc implant controls retinal inflammation effectively, choroidal inflammation would require alternative treatment.

Managing a patient with uveitis in the era of artificial intelligence: Current approaches, emerging trends, and future perspectives.

The integration of artificial intelligence (AI) with healthcare has opened new avenues for diagnosing, treating, and managing medical conditions with remarkable precision. Uveitis, a diverse group of rare eye conditions characterized by inflammation of the uveal tract, exemplifies the complexities in ophthalmology due to its varied causes, clinical presentations, and responses to treatments. Uveitis, if not managed promptly and effectively, can lead to significant visual impairment. However, its management requires specialized knowledge, which is often lacking, particularly in regions with limited access to health services. AI's capabilities in pattern recognition, data analysis, and predictive modelling offer significant potential to revolutionize uveitis management. AI can classify disease etiologies, analyze multimodal imaging data, predict outcomes, and identify new therapeutic targets. However, transforming these AI models into clinical applications and meeting patient expectations involves overcoming challenges like acquiring extensive, annotated datasets, ensuring algorithmic transparency, and validating these models in real-world settings. This review delves into the complexities of uveitis and the current AI landscape, discussing the development, opportunities, and challenges of AI from theoretical models to bedside application. It also examines the epidemiology of uveitis, the global shortage of uveitis specialists, and the disease's socioeconomic impacts, underlining the critical need for AI-driven approaches. Furthermore, it explores the integration of AI in diagnostic imaging and future directions in ophthalmology, aiming to highlight emerging trends that could transform management of a patient with uveitis and suggesting collaborative efforts to enhance AI applications in clinical practice.

Fluocinolone acetonide 0.2 µg/day intravitreal implant in non-infectious uveitis affecting the posterior segment: EU expert user panel consensus-based clinical recommendations.

BACKGROUND: Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants. METHODS: A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS. RESULTS: The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice. CONCLUSIONS: As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes.

Posner-Schlossman Syndrome European Study Group: study protocol and baseline patients characteristics of a multicentre study.

BACKGROUND: The aim of the Posner-Schlossman Syndrome European Study Group (PSS-ESG) is to acquire a comprehensive dataset of European patients with PSS. Here, we present the first report on the study protocol and the clinical findings of the patients at baseline. METHODS: The PSS-ESG is a retrospective, multicentre study designed to evaluate patients with PSS. The study, designed and driven by a European Expert Committee includes three datasets: (1) the baseline, (2) the follow-up and (3) the intraocular pressure (IOP)/glaucoma dataset. RESULTS: A total of 11 centres adhered to the PSS-ESG and 107 patients were included (68 males, 39 females) mostly Caucasian (93.4%). At uveitis onset, the patient's age ranged between 11 and 76 years, (mean age: 42±15 years).Best-corrected visual acuity was >0.5 in 80.3% of the eyes, IOP was >40 mm Hg in 44% of the eyes. Keratic precipitates were found in 78.5% of the eyes. No flare or cells in anterior chamber were detected in 56% and 53% of the cases, respectively. PCR analysis on aqueous sample was positive for cytomegalovirus-DNA in 50.6% out of the 81 tested patients. CONCLUSIONS: The PSS-ESG is the first multicentre study aimed to collect a comprehensive dataset of patients with PSS in non-Asian countries. A middlde-aged Caucasian male with a low-grade anterior chamber inflammation, keratic precipitates, preserved visual acuity and marked increased in IOP seemed to be the standard PSS patient across the 11 uveitis and glaucoma centres participating in the PSS-ESG.

Infectious eye disease in the 21st century-an overview.

Infectious diseases affecting the eye often cause unilateral or asymmetric visual loss in children and people of working age. This group of conditions includes viral, bacterial, fungal and parasitic diseases, both common and rare presentations which, in aggregate, may account for a significant portion of the global visual burden. Diagnosis is frequently challenging even in specialist centres, and many disease presentations are highly regional. In an age of globalisation, an understanding of the various modes of transmission and the geographic distribution of infections can be instructive to clinicians. The impact of eye infections on global disability is currently not sufficiently captured in global prevalence studies on visual impairment and blindness, which focus on bilateral disease in the over-50s. Moreover, in many cases it is hard to differentiate between infectious and immune-mediated diseases. Since infectious eye diseases can be preventable and frequently affect younger people, we argue that in future prevalence studies they should be considered as a separate category, including estimates of disability-adjusted life years (DALY) as a measure of overall disease burden. Numbers of ocular infections are uniquely affected by outbreaks as well as endemic transmission, and their control frequently relies on collaborative partnerships that go well beyond the remit of ophthalmology, encompassing domains as various as vaccination, antibiotic development, individual healthcare, vector control, mass drug administration, food supplementation, environmental and food hygiene, epidemiological mapping, and many more. Moreover, the anticipated impacts of global warming, conflict, food poverty, urbanisation and environmental degradation are likely to magnify their importance. While remote telemedicine can be a useful aide in the diagnosis of these conditions in resource-poor areas, enhanced global reporting networks and artificial intelligence systems may ultimately be required for disease surveillance and monitoring.

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness-a protocol for a randomised controlled trial (ASTUTE trial).

INTRODUCTION: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care. METHODS AND ANALYSIS: The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted. ETHICS AND DISSEMINATION: The trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available. TRIAL REGISTRATION: ISRCTN31474800. Registered 14 April 2020.

Fundus topographical distribution patterns of ocular toxoplasmosis.

BACKGROUND: To establish topographic maps and determine fundus distribution patterns of ocular toxoplasmosis (OT) lesions. METHODS: In this retrospective study, patients who presented with OT to ophthalmology clinics from four countries (Argentina, Turkey, UK, USA) were included. Size, shape and location of primary (1°)/recurrent (2°) and active/inactive lesions were converted into a two-dimensional retinal chart by a retinal drawing software. A final contour map of the merged image charts was then created using a custom Matlab programme. Descriptive analyses were performed. RESULTS: 984 lesions in 514 eyes of 464 subjects (53% women) were included. Mean area of all 1° and 2° lesions was 5.96±12.26 and 5.21±12.77 mm2, respectively. For the subset group lesions (eyes with both 1° and 2° lesions), 1° lesions were significantly larger than 2° lesions (5.52±6.04 mm2 vs 4.09±8.90 mm2, p=0.038). Mean distances from foveola to 1° and 2° lesion centres were 6336±4267 and 5763±3491 µm, respectively. The majority of lesions were found in temporal quadrant (p<0.001). Maximum overlap of all lesions was at 278 µm inferotemporal to foveola. CONCLUSION: The 1° lesions were larger than 2° lesions. The 2° lesions were not significantly closer to fovea than 1° lesions. Temporal quadrant and macular region were found to be densely affected underlining the vision threatening nature of the disease.

Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network.

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.

Ocular inflammatory events following COVID-19 vaccination: reporting of suspected adverse drug reactions to regulatory authorities in the UK.

BACKGROUND/AIMS: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published suspected adverse drug reactions to vaccines against COVID-19. Ocular inflammatory events following COVID-19 vaccination have been reported worldwide. METHODS: We analysed MHRA data on spontaneous reports of suspected ocular inflammatory events following COVID-19 vaccination between January 2021 and September 2022. RESULTS: The MHRA received 300 UK spontaneous suspected reports of ocular inflammatory events following COVID-19 vaccination, with a calculated prevalence of 6.6 events per 1 000 000 vaccinated individuals. Anterior uveitis was the most common phenotype (58.3%), followed by optic neuritis in 39.3%. Median number of days between vaccination and onset was 8 days. Resolution of the event was seen in 52.3%. CONCLUSION: Ocular inflammatory events following COVID-19 vaccination have a very rare prevalence in the UK. There is no increase in the reporting rate of uveitis, optic neuritis and scleritis following COVID-19 vaccination when compared with the range of incidence in the UK population. The Yellow Card System represents a vital instrument within the domain of pharmacovigilance, empowering patients and healthcare professionals to contribute to the ongoing monitoring of medication safety.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis.

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.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2-global current practice patterns for the management of Cytomegalovirus anterior uveitis.

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.

Antiviral treatment for acute retinal necrosis: A systematic review and meta-analysis.

Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).

Gains in the current understanding of managing neovascular AMD with brolucizumab.

BACKGROUND: Unresolved retinal fluid and high injection burden are major challenges for patients with neovascular age-related macular degeneration. Brolucizumab addresses these challenges by providing robust vision gains and superior fluid resolution, with the potential for longer treatment intervals. Brolucizumab has been associated with adverse events of retinal vasculitis and retinal vascular occlusion typically in the presence of intraocular inflammation (IOI). To define the incidence of the adverse events, Novartis convened an external safety review committee, which found a rate of 4.6% for definite or probable IOI, 3.3% for retinal vasculitis, and 2.1% for retinal vascular occlusion in the HAWK and HARRIER trials. Novartis also established a coalition to explore 4 areas regarding the adverse events: root cause, patient characterization, event mitigation and vigilance, and treatment protocols for the adverse events. Based on the coalition findings, a risk mitigation framework was developed. Prior to initiating treatment with brolucizumab, it is important to weigh the potential benefit against risk of adverse events and to consider patient risk factors such as prior history of IOI and/or retinal vascular occlusion. To mitigate the potential for IOI-related adverse events, it is important to conduct a thorough dilated eye examination before each injection and closely monitor patients throughout treatment. Patients should be educated on symptoms of IOI to monitor for. Brolucizumab should not be injected in the presence of active IOI. If an adverse event is identified, prompt and intensive treatment should be considered. CONCLUSION: Progress has been made in understanding how to mitigate IOI-related adverse events following treatment with brolucizumab.

Ocular sarcoidosis in adults and children: update on clinical manifestation and diagnosis.

Sarcoidosis-associated uveitis, is the predominant ocular sarcoidosis presentation, which affects both adults and children. For adults, international ocular sarcoidosis criteria (IWOS) and sarcoidosis-associated uveitis criteria (SUN) are defined. However, for children they are not yet established internationally. Due to the specificity of pediatric manifestations of sarcoidosis, this task is even more challenging. In children, sarcoidosis is subdivided into Blau syndrome and early-onset sarcoidosis (BS/EOS) affecting younger children (< 5 years) and the one affecting older children with clinical presentation resembling adults. Differential diagnosis, clinical work-up as well as diagnostic criteria should be adapted to each age group. In this article, we review the clinical manifestation of sarcoidosis-associated uveitis in adults and children and the sensitivity and specificity of various ocular sarcoidosis diagnostic modalities, including chest X-ray and CT, FDG PET-CT, gallium-67 scintigraphy, bronchoalveolar lavage fluid, genetic testing for NOD2 mutations and serum biomarkers, such as ACE, lysozyme and IL2R.

Cytomegalovirus anterior uveitis and occlusive retinal vasculitis without retinitis in a patient on immunomodulatory therapy.

PURPOSE: To describe unusual clinical features and therapeutic management of a case of cytomegalovirus (CMV) ocular disease in a patient on immunomodulatory therapy. SETTING/VENUE: Moorfields Eye Hospital NHS Foundation Trust, London, UK. METHODS: Medical history, clinical findings, investigation results, and multimodal imaging were retrospectively collected. RESULTS: A 61-year-old, South-East Asian man, developed CMV-related endotheliitis and occlusive retinal vasculitis, diagnosed by wide-angle fluorescein angiography. No retinitis was present on the fundus examination. Suspicion of CMV etiology was based on anterior segment findings, especially the presence of coin-shaped endothelial lesions. The diagnosis was confirmed by aqueous polymerase chain reaction (PCR) analysis which was positive for CMV DNA. The combined use of topical and systemic valganciclovir resulted in significant improvement of the picture. CONCLUSIONS: CMV can manifest in the eye as occlusive retinal vasculitis without the presence of typical retinitis.

Demystifying Ocular Syphilis - A Major Review.

Syphilis, caused by the spirochaete, Treponema pallidum, continues to be a public health challenge globally with its rates steadily increasing in the past few years. The disease is transmitted through small breaks in the skin during sexual contact, or via congenital transmission in utero, either across the placenta or by contact with an active genital lesion during delivery. Estimated 5.7-6 million new cases are detected every year worldwide in the 15-49 years age group. An increased incidence has been reported in most populations with particular clusters in special groups like men who have sex with men, female sex workers, and their male clients. Ocular syphilis has a varied presentation and is considered a great mimicker in all cases of uveitis. The laboratory diagnosis of syphilis is predominantly based on serological tests including TPHA and VDRL. Parenteral penicillin is the cornerstone of treatment for all stages of ocular syphilis.