Temperature and local anthropogenic pressures limit stony coral assemblage viability in southeast Florida.

Climate change is viewed as the primary threat to coral reefs, with local pressures exacerbating coral cover decline. The consensus is that improving water quality may increase resilience, but disentangling water quality and temperature impacts is difficult. We used distance-based linear models and random forests to analyze spatiotemporal variation in benthic community structure and interannual changes in the coral assemblage, in relation to specific environmental metrics in Southeast Florida. Temperature accounted for most of the variation, recruitment doubled and interannual increases in coral abundance tripled when mean annual temperature reached 27 °C, until maximum temperatures exceeded 31 °C. Benefits associated with warmer temperatures were negated by poor water quality, as nutrient enrichment was related to increased macroalgal cover, reduced coral recruitment and higher coral partial mortality. We suggest reducing local pressures will contribute to reduced macroalgae and enhance coral recovery, but that temperature is the predominant influence on coral assemblages.

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.

Update on the systemic management of noninfectious uveitis in children and adolescents.

Noninfectious uveitis (NIU) in children and adolescents is a rare but treatable cause of visual impairment in children. Treatments for pediatric NIU and their side effects, along with the risks of vision loss and the need for long-term disease monitoring, pose significant challenges for young patients and their families. Treatment includes local and systemic approaches and this review will focus on systemic therapies that encompass corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and biological disease-modifying antirheumatic drugs (bDMARD). Treatment is generally planned in a stepwise approach. Methotrexate is well-established as the preferential csDMARD in pediatric NIU. Adalimumab, an antitumor necrosis factor (TNF) agent, is the only bDMARD formally approved for pediatric NIU and has a good safety and efficacy profile. Biosimilars are gaining increasing visibility in the treatment of pediatric NIU. Other bDMARD with some evidence in literature for the treatment of pediatric NIU include infliximab, tocilizumab, abatacept, rituximab and, more recently, Janus kinase inhibitors. Important aspects of managing children on these systemic therapies include vaccination issues, risk of infection, and psychological distress. Also, strategies need to address regarding primary nonresponse/secondary loss of response to anti-TNF treatment, biological switching, and monitoring regimens for these drugs. Optimal management of pediatric uveitis involves a multidisciplinary team, including specialist pediatric uveitis and rheumatology nurses, pediatric rheumatologists, psychological support, orthoptic and optometry support, and play specialists.

Intravitreal Fluocinolone 0.19mg Implant in the Management of Chronic Non-Infectious Uveitis: 12-Month Outcomes from a Single Tertiary Centre.

AIM: To present efficacy and safety of 0.19 mg fluocinolone acetonide insert (FAi) to treat chronic noninfectious uveitis (NIU) in a single referral center. METHODS: A retrospective observational clinical study of 11 eyes with NIU complicated by chronic cystoid macular edema (CMO). RESULTS: The main indication for treatment was chronic CMO in all 11 eyes. The mean central retinal thickness (CRT) at baseline was 435 µm ± 176, improving to 296 µm ± 67 at 12 months. Raised intraocular pressure (IOP) was the commonest adverse event. An IOP >21 mmHg was observed in three eyes, and >30 mmHg in one eye, managed with topical therapy. The mean best corrected visual acuity (BCVA) was stable at 12 months. There were no observed recurrences of uveitis. Two eyes received adjunctive treatment for worsening CRT. CONCLUSIONS: Our results suggest FAi is an effective maintenance treatment for NIU with favorable functional and anatomical outcomes.

Avascular Necrosis of Bone in Patients with Uveitis Treated with Systemic Corticosteroids.

PURPOSE: To identify the prevalence, risk factors and outcomes of avascular necrosis (AVN) in patients with chronic uveitis. METHODS: A retrospective study of patients with corticosteroid-induced AVN treated at Manchester Uveitis Clinic between 1991 and 2019. RESULTS: From a cohort of 4478 patients, 1698 had been treated with systemic corticosteroids. Five patients with AVN were identified (prevalence 0.29%). The mean age at diagnosis of AVN was 49 years. All 5 patients were using systemic immunosuppression. Four patients developed femoral head AVN in 7 joints, one had bilateral knee osteonecrosis. The mean duration of corticosteroid before AVN was 38 months; the mean dose at onset was 17mg/day and the mean cumulative dose was 18,860mg. Three patients required total hip replacements but management was conservative for others. There was no permanent disability. CONCLUSIONS: AVN is a rare but severe complication of corticosteroid therapy. Clinicians should be vigilant for symptoms of bone pain as early detection and cessation of corticosteroids can reverse incipient AVN and avoid surgery.

Ocular Involvement in the Histiocytoses: A Literature Review with an Illustrative Case Series.

PURPOSE: To describe and illustrate recent reclassification and clinical descriptions of the histiocytoses, diagnosis and management, and effects on the eye and adnexae. PATIENTS AND METHODS: Literature review with an illustrative case series of seven patients with histiocytosis and ophthalmic involvement from a single tertiary centre. RESULTS: Skin lesions with signs including eyelid mass, orbital bone destruction, bizarre keratic precipitates, limbal or iris mass, haemorrhagic anterior uveitis, subretinal lesions of uncertain etiology, ischaemic retinopathy, optic neuropathy, and apparent steroid-resistant inflammations should be comprehensively investigated. CONCLUSIONS: Ophthalmic involvement in histiocytosis is rare. Clinical manifestations vary from limited single-organ disease to lethal systemic infiltration or malignancy. Radiology may identify lesions for biopsy. Histology with appropriate markers is essential. Oncology advice may be required.

Temperature stress and disease drives the extirpation of the threatened pillar coral, Dendrogyra cylindrus, in southeast Florida.

Rare species population dynamics can elucidate the resilience of an ecosystem. On coral reefs, climate change and local anthropogenic stressors are threatening stony coral persistence, increasing the need to assess vulnerable species locally. Here, we monitored the threatened pillar coral, Dendrogyra cylindrus, population in southeast Florida, USA, in relation to consecutive heat stress events in 2014 and 2015. In the fall of each year, D. cylindrus colonies bleached following intense thermal stress and by June 2020 all monitored colonies died from a white-syndrome type disease. This resulted in the ecological extinction of D. cylindrus in the Southeast Florida Coral Reef Ecosystem Conservation Area (ECA). White-syndrome type disease was first seen in February 2014 on four colonies (19% prevalence) near the major international port, Port Everglades and disease prevalence peaked in fall 2015 (58%). Disease prevalence increased with maximum water temperature, while disease related mortality increased with mean water temperature. Our findings suggest that thermal stress exacerbated underlying stony coral disease, resulting in an outbreak contributing to the ecological extirpation of D. cylindrus in the ECA. We suggest that stony coral resilience is severely compromised by chronic environmental disturbance which hinders community recovery.

Consensus Recommendations for the Diagnosis of Vitreoretinal Lymphoma.

PURPOSE: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). METHODS: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. RESULTS: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. CONCLUSIONS: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

Evaluating the Safety, Efficacy and Patient Acceptability of Intravitreal Fluocinolone Acetonide (0.2mcg/Day) Implant in the Treatment of Non-Infectious Uveitis Affecting the Posterior Segment.

Long-acting, slow-release injectable fluocinolone intravitreal implants have been approved for the treatment of non-infectious uveitis affecting the posterior segment. We summarise the development of intravitreal fluocinolone implants and discuss the technology including pharmacokinetics. We conducted a systematic review of evidence for the efficacy, safety and patient acceptability of fluocinolone 0.18 mg and 0.19 mg injectable implants. We summarise evidence from the pivotal phase 3 studies that lead to the approval of these implants and evaluate real-world including disease-specific evidence. Safety including injection-related events and long-term adverse events is presented.

Corneal Decompensation in Uveitis Patients: Incidence, Etiology, and Outcome.

Purpose: To identify the prevalence, etiology, management and visual outcomes of treatment in uveitis-related corneal decompensation.Patients and methods: This is a retrospective study of patients with corneal decompensation identified from a large cohort with uveitis in a tertiary referral clinic setting.Results: Between March 1991 and May 2018, 4132 new patients with uveitis were seen in Manchester Uveitis Clinic. Of these, 25 patients (0.6%) were identified with corneal decompensation of which 9 (0.2%) were affected bilaterally (total 34 eyes). The mean interval between uveitis diagnosis and decompensation was 23 months (range 0-117 m). Ten patients (41%) had associated glaucoma. Seventeen eyes (50%) had undergone intraocular surgery prior to decompensation. For eyes with no history of raised intraocular pressure or intraocular surgery, keratouveitis (presumed autoimmune or tuberculous) was the most common cause of corneal decompensation. Fourteen eyes (41%) required corneal graft and of these, five required repeat grafting.Conclusions: Corneal decompensation in eyes with uveitis is a rare but significant complication. Direct endothelial inflammation may alone cause decompensation, but in most eyes with uveitis, prior raised intraocular pressure or intraocular surgery are required to precipitate the cornea into decompensation. Outcomes of corneal transplantation in this group may be disappointing.

Immunosuppression in the Management of Presumed Non-infective Uveitis; Are We Sure What We are Treating? Notes on the Antimicrobial Properties of the Systemic Immunosuppressants.

PURPOSE: To describe the antimicrobial effects of immunosuppressants used for presumed autoimmune uveitis, and to discuss the potential importance of these effects in the context of increasing knowledge of the human microbiomes and their influence on inflammation. METHODS: Literature review. REVIEW OF EVIDENCE: All immunosuppressants have intrinsic antimicrobial effects; these vary considerably between drugs, and include antibacterial, antiviral and antifungal action. Immunosuppression is known to affect the composition of the gut microbiome, and alterations in microbiome composition are known to affect inflammations including uveitis. CONCLUSIONS: Oral immunosuppressants are assumed to act on presumed autoimmune uveitis by downregulation of, or other interference with, an aberrant immune response. However, their antimicrobial properties are usually forgotten, and in the context of increasing knowledge of the involvement of microbes in the initiation of, and also potentially the perpetuation of, tissue inflammation, these effects may prove to be a fundamental part of their action.

Intra and inter-rater agreement of inflammatory choroidal neovascular membrane measurements using optical coherence tomography angiography.

PURPOSE: Automated measurement algorithm software is not routinely available in optical coherence tomography angiography (OCTA) devices and manual measurement of choroidal neovascular membrane (CNVM) size is necessary. Our aim was to determine intra- and inter-rater agreement of inflammatory CNVM manual measurements obtained with OCTA. METHODS: OCTA (Triton® Topcon Corporation) images in patients with inflammatory CNVM were imported into ImageJ software v1.50 (NIH image). Two experienced observers performed manual area and perimeter measurements independently, and one of the observers performed the same measurements twice. Agreement was evaluated with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC). Bland-Altman plots were plotted to graphically assess concordance. Statistical analysis was performed using STATA v13.0. RESULTS: Sixteen eyes of 16 subjects, with a mean age of 39.0 ± 16.6 years (range 13-71), were included. Mean CNVM area and perimeter was 124.83 ± 117.80 and 4.20 ± 2.00 mm, respectively. Intra-rater ICC for both area and perimeter measured was 0.99 (95% confidence interval (CI) 0.99-0.99). Inter-rater ICC for area and perimeter measured was 0.95 (95%CI 0.87-0.98) and 0.81 (95%CI 0.17-0.94), respectively. Intra-rater CCC for both area and perimeter measured was 0.99 (95%CI 0.99-0.99). Inter-rater CCC for both area and perimeter measured was 0.91 (95%CI 0.81-0.99) and 0.66 (95%CI 0.44-0.88), respectively. CONCLUSIONS: Inflammatory CNVM manual measurement showed high intra-rater agreement and moderate inter-rater agreement. Repeatability and reproducibility studies are essential in manual analysis to establish thresholds that can distinguish measurements variation from true clinical change. An automatic algorithm may be helpful to accurately grade lesions and monitor disease activity and response to treatment.

Urgent Management of Secondary Glaucoma in Uveitis Using the Xen-45 Gel Stent.

PRECIS: The Xen-45 implant is an effective and safe treatment option for patients with medically uncontrolled glaucoma in the setting of uveitis, including those where urgent surgical intervention is required. PURPOSE: The purpose of this study was to report the efficacy and safety of the Xen-45 gel stent in eyes with glaucoma secondary to uveitis. METHODS: Retrospective observational case series of 37 eyes, with medically uncontrolled glaucoma in uveitis using Xen-45 implantation. All patients had at least 12 months follow-up. Primary outcome measures included visual acuity, intraocular pressure (IOP), degree of inflammation and ocular hypotensive medications. In addition, the time taken from the decision to surgery was recorded. Data were collected preoperatively and 1 day, 1 week, 1, 3, 6, and 12 months postoperatively. Postoperative complications included hypotony and decompressive retinopathy. The requirement for further glaucoma surgery, including bleb needling, and failure were documented. RESULTS: The mean follow-up time was 16.7 months (range: 12 to 32 mo). Preoperatively all patients were on >3 ocular hypotensive medications and 75.7% were on oral acetazolamide. Systemic immunosuppression was used in 62.2% and all were on topical steroids. Mean preoperative IOP was 36.1 mm Hg (±SD 9.6) on an average 3.69 (±SD 0.47) drops. The median time from decision to operate to surgery was 5.5 days (range: 1 to 120 d). Mean postoperative IOP was 12.6 mm Hg (±SD 4.1) with an average 0.62 (±SD 1.1) drops at 1 year representing a 65% drop in IOP and 83% reduction in IOP-lowering medication. Bleb needling with 5-fluorouracil was performed on 5 eyes (13.5%). Symptomatic hypotony occurred in 7 eyes requiring further interventions. No decompressive retinopathy was found at last follow-up. Five eyes (13.5%) failed, needing drainage tube surgery or trabeculectomy. CONCLUSIONS: The Xen-45 implant is an effective treatment for hypertensive crises in glaucoma in uveitis, offering dramatic IOP lowering without significant uveitis flare-up. In this group of patients with uveitis, needling rates are lower than reported in primary open-angle glaucoma. However, complications including hypotony can still occur.

Multimodal Evaluation of Presumed Tuberculous Serpiginous-Like Choroiditis.

Purpose: To evaluate multimodal imaging findings in longitudinal follow-up of a patient with presumed tuberculous serpiginous-like choroiditis (TB-SLC). Method: We evaluated multimodal imaging in a 62-year-old male with TB-SLC. Correlation between optical coherence tomography angiography (OCTA), swept-source OCT (SS-OCT) and fundus autofluorescence (FAF) at defined disease stages and evolution of observed imaging descriptors during long-term follow-up has not been previously reported. Results: OCTA of the active lesion demonstrated defined areas of choriocapillaris hypoperfusion, suggesting inflammatory vascular occlusive pathology. Over 9-month follow-up, OCTA illustrated sequential improvement in choriocapillaris flow, suggesting vascular remodeling. This correlated with progressive change in FAF signal and transition to diffuse hypoautofluorescence. SS-OCT demonstrated focal choroidal thickening and retinal pigment epithelium elevation in acute phase and resolution in time. Conclusion: Multimodal imaging, particularly novel non-invasive technologies such as OCTA and SS-OCT, improves our understanding of the pathogenesis and evolution of disease in TB-SLC.

Long-Term Outcomes and Complications of Baerveldt Glaucoma Drainage Implants in Adults with Glaucoma Secondary to Uveitis.

Purpose: This study investigated the efficacy and safety of Baerveldt glaucoma implants (BGI) in adults with uveitic glaucoma (UG) at the Manchester Uveitis Clinic.Methods: This was a retrospective study of 42 patients with UG who underwent BGI implantation between 2006 and 2015. Primary outcome measures were intraocular pressure (IOP) reduction and number of medications at 5-year follow-up. Three IOP success criteria were chosen: 1.IOP ≤21 mmHg and ≥20% reduction from baseline 2.IOP ≤17 mmHg and ≥20% reduction from baseline and 3.IOP ≤14 mmHg.Results: The mean pre-operative IOP was 29.5 ± 9.5 mmHg on 3.9 antiglaucoma drops. At 5-year follow-up, IOP reduced to 14.4 ± 7.0 mmHg (p < 0.005) on 1.4 drops. The cumulative probability of failure at 5 years based on criteria 1, 2, and 3 was 24.3%, 39.6%, and 56.3%, respectively.Conclusion: This study demonstrated that BGI are safe and effective in refractory UG, especially in younger adults with complex uveitis.

Certification of Vision Impairment in Patients with Uveitis Attending a Specialist Clinic.

Purpose: To identify the causes of severe visual loss in a UK uveitis clinic, to suggest means of reducing incidence, and to propose improvement in data collection of vision impairment. Patients and methods: Retrospective case series. Results: Over 128 months, 76 (3.5-4% of patients referred) were certified as vision-impaired or severely vision-impaired. The mean age at registration was 48.4 years, 76% were of working age, and 7% were children. The diagnosis leading most often to registration was sympathetic ophthalmia and the most frequent uveitis complications were secondary cataract (whether or not operated upon) in 62%, chronic cystoid macular edema in 43%, and secondary glaucoma in 28%. Visual loss was often multifactorial. Conclusions: Severe and permanent visual loss in uveitis affects people predominantly of working age. It is probably underreported and a restructuring of the certificate of vision impairment may improve data collection. Early referral to a tertiary center may reduce the incidence of vision impairment.