Ocular syphilis in patients with nonreactive RPR and positive treponemal serologies: a retrospective observational cohort study.

BACKGROUND: Screening for syphilis increasingly relies on positive treponemal rather than nontreponemal tests (rapid plasma reagin [RPR]). We compared ocular syphilis in patients with nonreactive versus positive RPR. METHODS: We conducted a retrospective observational cohort study of ocular syphilis treated at two New England hospitals 1996-2021 based on ophthalmologist-diagnosed eye findings and positive treponemal serology, regardless of RPR. We excluded patients with alternative diagnoses. We categorized RPR into nonreactive RPR, low-titer RPR (<1:8), and high-titer RPR (≥1:8) and compared early and long-term response to therapy. RESULTS: Our sample included 115 patients with ocular syphilis (median follow-up 2.5 years): 25 (22%) nonreactive RPR, 21 (18%) low-titer RPR, 69 (60%) high-titer RPR. Compared with nonreactive and low-titer RPR, people with high-titer RPR were younger (mean 47 years, p<0.001), more likely male (93%, p<0.001) and more likely to be living with HIV (49%, p<0.001). People with nonreactive and low-titer RPR were less likely than high-titer RPR to have posterior/panuveitis (32% and 29% versus 75%, p<0.001) or abnormal CSF (26% and 35% versus 75%, p<0.001), and more likely to present with chronic eye findings (20% and 29% versus 1%, p<0.001). In long-term follow up, eye findings improved and did not recur in most patients (62% nonreactive, 68% low-titer, 96% high-titer RPR); improved but recurred in 29%, 11%, and 4%, respectively; and were stable in 10%, 21%, and 0%, respectively. CONCLUSION: Patients with ocular syphilis and nonreactive RPR are similar to patients with low-titer RPR, and antibiotic therapy is beneficial in most.

Malignancy Risk Associated With the Use of Systemic Immunomodulatory Therapy in the Management of Noninfectious Uveitis.

PURPOSE: Patients with noninfectious uveitis (NIU) can require treatment with systemic immunomodulatory therapy (IMT), but it is unclear whether IMT drug categories increase the risk of malignancy in NIU patients. The purpose of this study is to determine if the use of systemic IMT in patients with NIU is associated with an increased risk of malignancy. DESIGN: Clinical cohort study. METHODS: Patients were identified from a US administrative medical claims database including some Medicare Advantage and commercial plans, from 2000 to 2022. About 318,498 NIU patients were identified. Enrollees were included in the analysis if they met the following criteria: continuous enrollment in the plan for at least 1 year, and at least 2 consecutive visit diagnoses of any type of NIU, after initiation of systemic IMT. We compared the rates of incident malignancy in NIU patients treated with IMT versus the rates among NIU patients not treated with IMT. Multivariable Cox regression models were used to predict the hazard of developing incident cancer. RESULTS: Of the 318,498 patients with NIU identified over a 15-year period, 318,006 did not develop malignancy, and 492 did develop malignancy. Of the patients that developed a malignancy, 280 (57%) were treated with systemic corticosteroids; 204 (41%) were treated with antimetabolites; 44 (9%) were treated with T cell inhibitors; 108 (22%) were treated with TNF alpha inhibitors; 2 (0.004%) were treated with interleukin-6 (IL-6) inhibitors; and 1 was treated with CD-20 antibodies. There were no malignancies reported in the group treated with alkylating agents. There was no association between any of the drug classes and incidence of malignancy. CONCLUSIONS: This study suggests that there is no increased risk of malignancy associated with the use of systemic IMT for patients with NIU.

The prophylactic value of TNF-α inhibitors against retinal cell apoptosis and optic nerve axon loss after corneal surgery or trauma.

BACKGROUND AND PURPOSE: Late secondary glaucoma is an often-severe complication after acute events like anterior segment surgery, trauma and infection. TNF-α is a major mediator that is rapidly upregulated, diffusing also to the retina and causes apoptosis of the ganglion cells and degeneration of their optic nerve axons (mediating steps to glaucomatous damage). Anti-TNF-α antibodies are in animals very effective in protecting the retinal cells and the optic nerve-and might therefore be useful prophylactically against secondary glaucoma in future such patients. Here we evaluate (1) toxicity and (2) efficacy of two TNF-α inhibitors (adalimumab and infliximab), in rabbits by subconjunctival administration. METHODS: For drug toxicity, animals with normal, unburned corneas were injected with adalimumab (0.4, 4, or 40 mg), or infliximab (1, 10, or 100 mg). For drug efficacy, other animals were subjected to alkali burn before such injection, or steroids (for control). The rabbits were evaluated clinically with slit lamp and photography, electroretinography, optical coherence tomography, and intraocular pressure manometry. A sub-set of eyes were stained ex vivo after 3 days for retinal cell apoptosis (TUNEL). In other experiments the optic nerves were evaluated by paraphenylenediamine staining after 50 or 90 days. Loss of retinal cells and optic nerve degeneration were quantified. RESULTS: Subconjunctival administration of 0.4 mg or 4.0 mg adalimumab were well tolerated, whereas 40.0 mg was toxic to the retina. 1, 10, or 100 mg infliximab were also well tolerated. Analysis of the optic nerve axons after 50 days confirmed the safety of 4.0 mg adalimumab and of 100 mg infliximab. For efficacy, 4.0 mg adalimumab subconjunctivally in 0.08 mL provided practically full protection against retinal cell apoptosis 3 days following alkali burn, and infliximab 100 mg only slightly less. At 90 days following burn injury, control optic nerves showed about 50% axon loss as compared to 8% in the adalimumab treatment group. CONCLUSIONS: Subconjunctival injection of 4.0 mg adalimumab in rabbits shows no eye toxicity and provides excellent neuroprotection, both short (3 days) and long-term (90 days). Our total. accumulated data from several of our studies, combined with the present paper, suggest that corneal injuries, including surgery, might benefit from routine administration of anti-TNF-α biologics to reduce inflammation and future secondary glaucoma.

Concurrence of Ocular Cicatricial Pemphigoid in Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: The aim of this study was to report a series of 3 patients with ocular graft-versus-host disease (oGVHD) with progressive cicatricial conjunctival changes who were diagnosed with ocular cicatricial pemphigoid (OCP) after conjunctival biopsy. METHODS: This study was a retrospective case series. RESULTS: Three patients who received hematopoietic stem cell transplantation for hematologic malignancies developed oGVHD and subsequently were diagnosed with OCP. Case 1 was a 73-year-old woman with oGVHD who developed symblepharon and showed positive IgA, IgG, and C3 staining of the basement membrane zone (BMZ) on conjunctival biopsy, consistent with OCP. She was systemically treated with tacrolimus and prednisone with resolution of conjunctival inflammation. Case 2 was a 68-year-old man with oGVHD who developed symblepharon, severe dry eye, and corneal epithelial defect. An initial conjunctival biopsy was negative, but a repeat biopsy performed 10 years later showed positive BMZ IgA and IgG staining. Healing of the epithelial defect was achieved after treatment with high-dose systemic cyclosporine. Case 3 was a 75-year-old woman with oGVHD who had a nonhealing corneal epithelial defect and symblepharon with positive IgA BMZ staining on conjunctival biopsy, consistent with OCP. The patient responded well to methotrexate with healing of the epithelial defect. CONCLUSIONS: Although low-grade conjunctival fibrotic changes may be observed in chronic oGVHD, development of severe and progressive cicatricial changes, including symblepharon formation, should prompt consideration of biopsy to rule out concurrent OCP, the management of which differs from that of oGVHD.

Incidence of and Risk Factors for Cataract in Anterior Uveitis.

PURPOSE: To estimate the incidence/risk factors for cataract in noninfectious anterior uveitis. DESIGN: Retrospective multicenter cohort study (6 US tertiary uveitis sites, 1978-2010). METHODS: Data were harvested by trained expert reviewers, using protocol-driven review of experts' charts. We studied cataract incidence-newly reduced visual acuity worse than 20/40 attributed to cataract; or incident cataract surgery-in 3923 eyes of 2567 patients with anterior uveitis. RESULTS: Cataract developed in 507 eyes (54/1000 eye-years, 95% CI 49-59). Time-updated risk factors associated with cataract included older age (≥65 vs <18 years: adjusted hazard ratio [aHR] 5.04, 95% CI 3.04-8.33), higher anterior chamber cell grade (P(trend)=0.001), prior incisional glaucoma surgery (aHR 1.86, 95% CI 1.10-3.14), band keratopathy (aHR 2.23, 95% CI 1.47-3.37), posterior synechiae (aHR 3.71, 95% CI 2.83-4.87), and elevated intraocular pressure ≥30 vs 6-20 mm Hg (aHR 2.57, 95% CI 1.38-4.77). Primary acute (aHR 0.59, 95% CI 0.30-1.15) and recurrent acute (aHR 0.74, 95% CI 0.55-0.98) had lower cataract risk than chronic anterior uveitis. Higher-dose prednisolone acetate 1%-equivalent use (≥2 drops/day) was associated with >2-fold higher cataract risk in eyes with anterior chamber cell grades 0.5+ or lower but was not associated with higher cataract risk in the presence of anterior chamber cells of grade 1+ or higher. CONCLUSIONS: Cataract complicates anterior uveitis in ∼5.4/100 eye-years. Several fixed and modifiable risk factors were identified, yielding a point system to guide cataract risk minimization. Topical corticosteroids only were associated with increased cataract risk when anterior chamber cells were absent or minimally present, suggesting their use to treat active inflammation (which itself is cataractogenic) does not cause a net increase in cataract incidence.

High Positive Predictive Value of Fluorescein Angiography Contiguous, Perineural Retinal Vascular Leakage Pattern for Birdshot Chorioretinopathy.

PURPOSE: To determine the sensitivity and positive predictive value (PPV) of a contiguous, perineural retinal vascular leakage fluorescein angiography (FA) pattern in birdshot chorioretinopathy (BSCR) patients. METHODS: Patients with BSCR and other posterior uveitis/retinal vasculitis and a FA were identified. Two graders reviewed the first FA for leakage primarily around the optic nerve and along the larger arcade vessels. We compared the rates of this pattern in BSCR and non-BSCR patients and calculated sensitivity and PPV. We compared clinical characteristics of BSCR patients with and without this pattern. RESULTS: 64 BSCR and 98 non-BSCR patients were identified. The FA pattern's sensitivity, specificity, and PPV were 57.8%, 91.8%, and 82.2%. This pattern was significantly more common in BSCR patients earlier in their disease (p = .004). CONCLUSIONS: A contiguous, perineural retinal vascular leakage FA pattern can help identify potential BSCR patients for further testing. This pattern is more common closer to symptom onset.

Mendelian Randomization Shows a Causal Effect of Low Vitamin D on Non-infectious Uveitis and Scleritis Risk.

PURPOSE: To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. DESIGN: Two-sample Mendelian randomization case-control study. METHODS: The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated. RESULTS: We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR] = 2.16, 95% CI = 1.01-4.64, P = .049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06-5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19-12.89, P = 1.7 × 10-7, per SD of log25OHD). CONCLUSIONS: Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.

Anti-infliximab antibodies and clinical response in noninfectious uveitis and scleritis patients treated with infliximab: A retrospective review.

Purpose: To investigate the clinical response to infliximab in ocular inflammation patients who develop anti-infliximab antibodies (AIA) vs. those patients who do not develop AIA. Observations: A retrospective review was performed of patients treated with infliximab for noninfectious uveitis (NIU) or scleritis. Clinical response was determined as a composite clinical endpoint and classified as complete, partial, or absent. Nine of 32 infliximab-treated patients (28%) were found to develop AIA. Among the AIA-positive patients, clinical response was complete in 7 patients (78%) and partial in 2 patients (22%). Among the AIA-negative patients, clinical response was complete in 15 patients (65%), partial in 6 patients (26%) and absent in 2 patients (9%). Serum infliximab levels tended to decrease with appearance of AIA but rarely became undetectable. Conclusions and Importance: In this pilot study, AIA-positive patients did not have diminished clinical response to infliximab when compared with AIA-negative patients. There was a high rate of complete clinical response to infliximab in this group of NIU and scleritis patients. Approximately a quarter of patients developed AIA. AIA-positive patients did not have diminished rates of clinical response when compared with AIA-negative patients. This suggests that routine AIA monitoring may not be clinically useful, although validation of this finding in larger cohorts is necessary.

Restoration of Vision in Severe, Cicatricial, Ocular Surface Disease With the Boston Keratoprosthesis Type II.

PURPOSE: To assess clinical outcomes of patients with severe, cicatricial ocular surface disease (OSD) implanted with the currently marketed design of the Boston keratoprosthesis type II (BK2). DESIGN: Retrospective cohort study. METHODS: Records of consecutive patients undergoing BK2 implantation from June 2009 to March 2021 were assessed for postoperative visual acuity, postoperative complications, device replacement, and additional surgeries. RESULTS: Fifty-six eyes of 53 patients with a mean follow-up of 45.8 months (range, 0.2-134.7 months) were included. Stevens-Johnson syndrome/toxic epidermal necrolysis was the most common indication (49.1%), followed by mucous membrane pemphigoid (39.6%) and other OSD (11.3%). Visual acuity improved from logMAR 2.2 ± 0.5 preoperatively to 1.5 ± 1.2 at final follow-up. Of 56 eyes, 50 saw ≥20/200 at some point postoperatively. Of the eyes with a follow-up of more than 5 years, 50.0% retained a visual acuity of ≥20/200 at their final follow-up. The most common complications over the entire postoperative course (mean ∼4 years) were de novo or worsening glaucoma (41.1%), choroidal effusions (30.3%), retinal detachment (25.0%), and end-stage glaucoma (25.0%). In a univariate analysis, patients who experienced irreversible loss of ≥20/200 visual acuity were more likely to have been previously implanted with an older design of BK2, less likely to be on preoperative systemic immunosuppressive therapy, and less likely to have undergone concurrent glaucoma tube implantation, compared to patients who retained ≥20/200 acuity (P < .04 for all). CONCLUSIONS: Advances in device design and postoperative care have made implantation of BK2 a viable option for corneal blindness in the setting of severe cicatricial OSD.

Primary central nervous system lymphoma: Inter-compartmental progression.

There is limited understanding of the inter-compartmental progression and treatment outcomes of primary central nervous system lymphoma (PCNSL). In this multicenter retrospective cohort study on 234 patients with PCNSL (median age: 62.5 years [18-92]; median follow-up 35 months [0.1-237.0]) from 2000 till 2018 were divided into group 1 (ocular, 44 patients): 1A and 1B without and with CNS progression and group 2 (CNS, 190 patients): 2A and 2B without and with ocular progression, respectively. In group 1 (44 patients), 33 patients received local treatment, and 11 patients received systemic treatment. In group 2 (15 patients), six patients received combination treatment, while seven patients received only systemic treatment. A complete response was observed in 19 (43%) and 91 (48%) patients in groups 1 and 2, respectively. The 2-year progression-free survival (PFS) was 35% (95% CI: 0.23, 0.54) and 56% (95% CI: 0.49, 0.63) for groups 1 and 2, respectively (p < 0.0001). Age < 60 years was significantly associated with longer PFS (median PFS 48 vs. 24 months, p = 0.01). The overall survival (OS) at 2-year was similar among groups 1 and 2 (83% and 67%), respectively (p = 0.06). Thus, Initial compartment of involvement does not influence local response rate or OS.

Uveitis Specialists Harnessing Disruptive Technology during the COVID-19 Pandemic and Beyond.

Spurred by the coronavirus disease pandemic and shortage of eye care providers, telemedicine is transforming the way ophthalmologists care for their patients. Video conferencing, ophthalmic imaging, hybrid visits, intraocular inflammation quantification, and portable technology are evolving areas that may allow more uveitis patients to be evaluated via telemedicine. Despite these promising disruptive technologies, there remain significant technological limitations, legal barriers, variable insurance coverage for virtual visits, and lack of clinical trials for uveitis specialists to embrace telemedicine.

Comparison of Modified Posterior Sub-Tenon's vs. Trans-Septal Triamcinolone Injection for Non-infectious Uveitis.

Purpose: To compare the safety and efficacy of trans-septal vs. modified posterior sub-Tenon's (PST) corticosteroid injections for noninfectious uveitis.Methods: Retrospective comparison of periocular triamcinolone injection by modified PST (n = 36) vs. traditional trans-septal (n = 79) techniques. Safety and efficacy outcomes were analyzed with regression models.Results: There was no significant difference in visual acuity improvement between the groups at 6 months. There were higher rates of vitritis resolution in the modified PST group but this was not statistically significant (85.7% vs 62.9%, p = .07). Intraocular pressure (IOP) elevation rate trended higher with the modified PST injection (21.9% vs 9.0%, p = .06), with no instances of glaucoma surgery in either group. Two modified PST injection patients with refractory IOP rises had IOP normalization after corticosteroid depot removal. One year cataract surgery rates were similar.Conclusion: Modified PST injection offers clinical efficacy but with possibly higher IOP response rate which could be managed with corticosteroid removal.

Ocular Adverse Events following Use of Immune Checkpoint Inhibitors for Metastatic Malignancies.

PURPOSE: To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies. METHODS: Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy. RESULTS: Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs. CONCLUSION: We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.

Real-Time Multiplex PCR Analysis in Infectious Uveitis.

Introduction: Infectious uveitis is a serious inflammatory condition that often causes grave ocular morbidity including permanent vision loss and damage to the structures of the eye. The most common causes of infectious uveitis include herpesviruses and Toxoplasma gondii. Traditionally, these infections have been identified and differentiated based on characteristic clinical examination findings; however, there is often overlap between these presentations and the unique cause of a given patient's infection is not always clear. Therefore, a reliable and fast method for definitively diagnosing infectious uveitis would be helpful and potentially sight-saving. Several groups have recently found experimental success with real-time multiplex polymerase chain reaction (PCR) techniques. Methods: A comprehensive review of the literature was undertaken to further understand the current state of real-time multiplex PCR and its clinical use. Search terms including "real time multiplex PCR", "infectious uveitis", and "uveitis diagnosis" were used. Appropriate English-language articles were included in this review. Results: Publications from four main groups (two from the United States, one from Japan, and one from India) citing success with real-time multiplex PCR were compared and contrasted. All four groups used the same technique to develop a highly sensitive and specific multiplex PCR analysis and found that their tests maintained high sensitivity and specificity during validation testing. These tests confirmed clinical suspicions in the majority of cases of infectious uveitis, but there were also cases of clinical misdiagnosis that were corrected based on molecular pathogen detection. These patients were then initiated on appropriate antimicrobial therapy with subsequent clinical improvement. Discussion: Real-time multiplex PCR is a highly sensitive and specific laboratory assay that allows for rapid and reliable molecular diagnosis of causative agents in infectious uveitis. This in turn facilitates swift initiation of effective therapy and prevents long-term ocular damage and vision loss.

Association of Low Vitamin D Levels with Noninfectious Uveitis and Scleritis.

Purpose: To determine whether an association between Vitamin D and noninfectious ocular inflammation exists. Methods: Retrospective case-control study with 765 patients (333 uveitis cases, 103 scleritis cases, 329 controls). Logistic regression models examined the relationship between hypovitaminosis D and ocular inflammation. Results: The odds of having uveitis were 1.92 times higher for patients with hypovitaminosis D compared to patients with normal Vitamin D levels in the multivariate analysis [odds ratio (OR) = 1.92, 95% Confidence Interval (CI) = 1.36-2.72, p = 2.32 × 10-4]. A secondary analysis demonstrated that the odds of developing uveitis or scleritis were 5% lower and 4% lower, respectively, for every unit increase in Vitamin D level (uveitis: OR = 0.95, 95% CI = 0.94-0.97, p = 9.87 × 10-6; scleritis: OR = 0.96, 95% CI = 0.93-0.99, p = 0.009). Conclusion: Hypovitaminosis D was associated with increased risk of ocular inflammation in this retrospective study.

Association of genetic variants in RAB23 and ANXA11 with uveitis in sarcoidosis.

Purpose: Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis. Methods: Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK. Results: SNPs rs1040461 and rs61860052, in ras-related protein RAS23 (RAB23) and annexin A11 (ANXA11) genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in HLA-DRB5 and HLA-DRB1, were associated with uveitis as well (p=0.009 and p=0.04). Conclusions: Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk.

Cataract Surgery Complications in Uveitis Patients: A Review Article.

Uveitis is a leading causes of blindness worldwide, and the development of cataracts is common due to both the presence of intraocular inflammation and the most commonly employed treatment with corticosteroids. The management of these cataracts can be very challenging and often requires additional procedures that can compromise surgical results. The underlying disease affects a relatively young population at higher risk of complications. Preoperative control of inflammation/quiescent disease for at least three months is generally accepted as the minimum amount of time prior to surgical intervention. Phacoemulsification with intraocular lens is the preferred method for surgery, with some studies showing improvement in visual acuity in over 90% of patients. The most common postoperative complications include macular edema, posterior capsule opacification, recurrent or persistent inflammation, glaucoma, epiretinal membrane and IOL deposits, or dislocation. Despite the potential complications, cataract surgery in uveitis patients is considered a safe and successful procedure.

Chemical Burns of the Eye: The Role of Retinal Injury and New Therapeutic Possibilities.

PURPOSE: To propose a new treatment paradigm for chemical burns to the eye - in the acute and chronic phases. METHODS: Recent laboratory and clinical data on the biology and treatment of chemical burns are analyzed. RESULTS: Corneal blindness from chemical burns can now be successfully treated with a keratoprosthesis, on immediate and intermediate bases. Long term outcomes, however, are hampered by early retinal damage causing glaucoma. New data suggest that rapid diffusion of inflammatory cytokines posteriorly (TNF-α, etc) can severely damage the ganglion cells. Prompt anti-TNF-α treatment is markedly neuroprotective. Long term profound reduction of the intraocular pressure is also vital. CONCLUSION: A new regimen, in addition to standard treatment, for severe chemical burns is proposed. This involves tumor necrosis factor alpha (TNF-α) inhibition promptly after the accident (primarily for retinal neuroprotection), prophylactic maximal lowering of the intraocular pressure (starting immediately), and keratoprosthesis implantation in a later quiet state.