Sight-threatening Eye Disease Research Articles

Transnasal Approach to Urgent Decompression of Active, Sight-Threatening Thyroid Eye Disease

Transnasal Approach to Urgent Decompression of Active, Sight-Threatening Thyroid Eye Disease

Tocilizumabuse for optic nerve compression in thyroid eye disease: a prospective longitudinal cohort.

To assess the effectiveness of tocilizumab in reverting the signs and symptoms of dysthyroid optic neuropathy (DON) in thyroid eye disease and the need for emergency orbital decompression. The secondary outcomes are to identify the optimal number of tocilizumab cycles to achieve the primary outcome, to analyze the association between thyroid stimulating immunoglobulin (TSI), clinical activity score (CAS) and proptosis in response to the treatment and the need for rehabilitative orbital decompression. Prospective longitudinal cohort study that included 13 patients who had unilateral or bilateral dysthyroid optic neuropathy (DON) due to severe and progressive sight-threatening thyroid eye disease based on the CAS system. Patients were seen in this facility starting from July 2017, and all had received intravenous tocilizumab. Initial visual acuity mean was 0.52 ± 0.38 and the final were 0.93 ± 0.11 with a mean difference of 0.41 and P < 0.00245. The mean CAS prior to the initiation of the treatment was 7.92 ± 0.66 and the final was 2.85 ± 1.03 with mean difference of 5.07 and P < 0.00001. Initial mean proptosis was 24.85 ± 2.31 and the final was 21.78 ± 2.18 with a mean difference of 3.07 and P < 0.000497. No emergency orbital decompression was performed. TSI was high initially in all cases with a wide range of 2.4 to 40 IU/L and with a mean of 10.70 ± 13.40. The final TSI mean was 2.90 ± 3.90 with a mean difference of 7.81 and significant P value (P < 0.0272). Tocilizumab use in optic nerve compression showed promising results as it can be the primary or an alternative treatment option.

Real-World Experience in the Use of Immunosuppression for the Management of Inflammatory Eye Disease

ABSTRACT Purpose Patients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal. Methods Adult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behçet’s disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured. Results Out of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for ≥24 months. The median duration of remission was 4–5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner. Conclusion Progressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development.

P-65 A case of relapse of Graves ophthalmopathy due to an ophthalmic herpes zoster infection in a thyroidectomized patient with multiple comorbidities

Abstract Introduction Graves ophthalmopathy usually occurs in patients with hyperthyroidism or a history of Graves disease, but it can appear in euthyroid patients or patients with chronic thyroiditis also. It is a possible cause of sight-threatening eye disease. Its incidence is 16 for women and 3 cases for men, per 100 000 population but more severe in men, and it's higher among smokers. In mild forms, treatment can be local, but in severe cases and recurrences, systemic glucocorticoids are compulsory, with or without immunosuppressive drugs, surgery or radiotherapy. in recurrences. Clinical Case We present the case of a 76-year-old male, former smoker, diagnosed with Graves disease in 2017. He was treated with anti-thyroid treatment and in 2018 he was thyroidectomized. He also developed a progressive Graves ophthalmopathy from April to July 2017 with a reduced visual acuity for both eyes, conjunctival erythema, palpebral edema and erythema. He received methyl-prednisolone (MP) pulse therapy 6×125 mg weekly with favorable outcome. In 2019, he underwent a recession of internal rectus and inferior rectus for both eyes to correct a divergent strabism and his eye-sight improved. He presents now for an aggravation of the ophthalmopathy after an episode of a herpes zoster infection affecting the ophthalmic branch of the trigeminal nerve. He also suffers from heart failure NYHA III, permanent atrial fibrillation, large aortic stenosis, asymptomatic hyperuricemia, secondary pulmonary hypertension and chronic kidney disease stage IIIb. His medical history revealed hypercholesterolemia, hyperuricemia, heart failure, insufficient status of vitamin D3 and confirmed the chronic kidney disease stage IIIb; normal thyroid function but with high anti TSH receptor antibodies (TRAb=18.37 U/L). Given the age and the comorbidities but also the high activity of the Graves disease and the orbital CT that revealinged a great hypertrophy of the ocular muscles, our ophthalmologist suggested methyl-prednisolone pulse therapy in a standard regimen, but our cardiologist contradicted it because of the heart conditions. As the patient's left eye sight was only 2% and for the right one 20%, we decided to adapt the doses of the pulse therapy and closely monitor the patient. The first dose was 125mg MP, after that 7 doses of 250mg MP weekly was followed by 3 doses of 125mg MP weekly. After a total of 2250 mg MP at a 3 months follow-up, the patients’ eyesight improved to 60% on the left eye and 75% on the right eye and a lower level of TRAb=5.59 UI/L. Conclusion Even in patients with comorbidities where corticosteroid therapy may be detrimental, there is a possibility to adapt the doses in a safe way and with a continuous clinical monitoring so that the patients’ eyesight can be saved, therefore increasing the quality of life.

Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants.

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are neurotropic human alphaherpesviruses endemic worldwide. Upon primary infection, both viruses establish lifelong latency in neurons and reactivate intermittently to cause a variety of mild to severe diseases. Acute retinal necrosis (ARN) is a rare, sight-threatening eye disease induced by ocular VZV or HSV infection. The virus and host factors involved in ARN pathogenesis remain incompletely described. We hypothesize an underlying genetic defect in at least part of ARN cases. We collected blood from 17 patients with HSV-or VZV-induced ARN, isolated DNA and performed Whole Exome Sequencing by Illumina followed by analysis in Varseq with criteria of CADD score > 15 and frequency in GnomAD < 0.1% combined with biological filters. Gene modifications relative to healthy control genomes were filtered according to high quality and read-depth, low frequency, high deleteriousness predictions and biological relevance. We identified a total of 50 potentially disease-causing genetic variants, including missense, frameshift and splice site variants and on in-frame deletion in 16 of the 17 patients. The vast majority of these genes are involved in innate immunity, followed by adaptive immunity, autophagy, and apoptosis; in several instances variants within a given gene or pathway was identified in several patients. We propose that the identified variants may contribute to insufficient viral control and increased necrosis ocular disease presentation in the patients and serve as a knowledge base and starting point for the development of improved diagnostic, prophylactic, and therapeutic applications.

Vitamin D deficiency and development of complications in individuals with type 1 and type 2 diabetes: A cohort study

AimsTo investigate vitamin D deficiency as a risk marker for complications in individuals with type 1 and type 2 diabetes. MethodsA cohort study including 1448 adults with type 1 and 770 with type 2 diabetes. Individuals in the decile with lowest vitamin D level were classified as vitamin D deficient. Outcomes based on medical records and registers included mortality, major adverse cardiovascular event (MACE), heart failure, a composite kidney endpoint, albuminuria progression and sight-threatening eye disease. Risk in individuals with vitamin D deficiency was compared to the remaining using adjusted Cox proportional hazards models. ResultsVitamin D deficiency was associated with higher risk of MACE (adjusted hazard ratio (HR): 2.6; 95 % confidence interval (CI): 1.3–5.2) in type 1, but not in type 2 diabetes. Risk of heart failure was higher in individuals with vitamin D deficiency in both cohorts (HR (95%CI): 16 (4.8–50) in type 1 and 2.4 (1.1–5.5) in type 2 diabetes). Vitamin D deficiency was not associated with development of microvascular complications or mortality. ConclusionsVitamin D deficiency was a risk marker for MACE and heart failure in type 1 and for heart failure in type 2 diabetes, but not for microvascular complications or all-cause mortality.

Endotrophin as a risk marker of mortality and kidney complications in a type 1 diabetes cohort.

Hyperglycemia triggers pathological pathways leading to fibrosis, where extracellular matrix (ECM) components are accumulated. We investigated the potential of endotrophin, a pro-fibrotic molecule generated during collagen type VI formation, as a risk marker for complications to type 1 diabetes. Endotrophin was measured in serum and urine from 1,468 persons with type 1 diabetes. Outcomes included a composite kidney endpoint, first major adverse cardiovascular event (MACE), all-cause mortality, progression of albuminuria, incident heart failure, and sight-threatening diabetic eye disease. Cox proportional hazards models adjusted for conventional risk factors were applied. A doubling of serum endotrophin was independently associated with the kidney endpoint (n = 30/1,462; hazard ratio 3.39 [95% CI: 1.98-5.82]), all-cause mortality (n = 93/1,468; 1.44 [1.03-2.0]), and progression of albuminuria (n = 80/1,359; 1.82 [1.32-2.52]), but not with first MACE, heart failure, or sight-threatening diabetic eye disease after adjustment. Urinary endotrophin was not associated with any outcome after adjustment. Serum endotrophin was a risk marker for mortality and kidney complications in type 1 diabetes. Biomarkers of ECM remodeling, such as serum endotrophin, may identify persons with active pro-fibrotic processes at risk for complications in diabetes and where antifibrotic agents may reduce this risk.

Association between Sight-Threatening Eye Diseases and Death by Suicide in South Korea: A Nationwide Population-based Cohort Study

Although associations between visual impairment (VI) and suicide are posited, specific risks across the sight-threatening eye disease (STED) spectrum remain to be assessed. We determined whether individuals with STED die more often by suicide than do other people and assessed the temporal associations. A nationwide, population-based cohort study. All persons aged 40 years or older in South Korea from 2010 to2020. Persons diagnosed with STEDs (i.e., glaucoma, exudative age-related macular degeneration [AMD], or diabetic retinopathy [DR]) were identified in the Korean National Health Insurance (NHI) service database. Both NHI health checkup records and the National Disability Registration were used for coexisting severe VI. Death by suicide was defined as diagnostic codes as recorded in the Korea National Statistical Office. Incidence rate ratios (IRRs) were estimated by quasi-Poisson regressions and adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and VI. The temporal relationship between time since first STED diagnosis and suicide risk was determined by identifying patients with STED newly diagnosed during the period from 2010 to2011. The IRR of death by suicide in people with STED relative to those without. Of the 2.8 million people (45% male) observed for 24 300 969 person-years, 13 205 died by suicide. Among them, 34% (n= 4514) had a STED diagnosis, for a suicide rate of 69 per 100 000 person-years (95% confidence interval [CI], 67-72), relative to 51 per 100 000 person-years (95% CI, 50-52) for non-STED individuals. People with STED had an adjusted IRR of 1.33 (95% CI, 1.26-1.41) relative to those without. The largest excess adjusted IRR of suicide mortality was that for DR (1.40, 95% CI, 1.29-1.52). For exudative AMD, the adjusted IRR was 1.20 (95% CI, 1.04-1.39), whereas for glaucoma, the corresponding value was 1.09 (95% CI, 1.02-1.17). With coexisting severe VI, the IRR for any STED was 1.49 (95% CI, 1.29-1.73). The highest suicide hazard ratio was between 3 and 6 months postdiagnosis (5.33; 95% CI, 4.59-6.20). In South Korea between 2010 and 2020, a higher suicide rate was evident among those with diagnosed STED than for persons not so diagnosed. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ptosis in long standing VKC in young adults

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. Though medically treated, some complications of the disease like ptosis may require surgical intervention, thus identifying the association of ptosis with VKC is of utmost importance. This study was done to see the relation between long-standing VKC and acquired ptosis in young adults.This was a hospital based non-comparative, observational study, conducted in the department of Ophthalmology, SKIMS Medical College Hospital, and Srinagar from March 2020 to May 2022. 60 patients upto the age of 40 years with any form of VKC were included in the study. Ocular examination included visual acuity testing, slit lamp biomicroscopic examination to evaluate corneal and conjunctival involvement, proper history and evaluation of ptosis.Mean age of cases was 16.23± 6.97. Out of 60 patients maximum were in the age group of 10-15 years (31.66%), followed by the age group of 15-20 years (21.66%). Out of total 60 cases 46(76.66%) were male and 14(23.33%) were female. Palpebral form of the disease was seen to be in most of the cases 53.33%, followed by mixed form of the disease in 28.33% and bulbar disease in 18.33% of the cases. Presence of acquired ptosis as a complication due to VKC was seen in 9(15%) patients. Out of these 9 patients 7 patients presented with unilateral ptosis and 2 patients presented with bilateral ptosis. Average duration of symptoms in these patients was 5.0±1.8 years, indicating that ptosis is a complication of long standing VKC. All these patients had palpebral or mixed form of VKC, none had bulbar form of the disease.Our study revealed that prolonged severe VKC may induce a lower position of the upper eyelid and eventually lead to ptosis, which is a non-reversible complication of VKC and requires surgical correction. Thus better primary eye care for the management of VKC in children may prevent this complication.

Chinese expert consensus on ocular surface diseases related to topical glaucoma medications (2022)

Glaucoma is a chronic progressive sight-threatening eye disease, so most patients need long-term or even lifelong medications. The ocular surface diseases caused by the use of topical glaucoma medications seriously affect the treatment compliance, the quality of life, and the treatment effects. In order to standardize the diagnosis and treatment of topical glaucoma medications-related ocular surface diseases, to improve the ocular surface health of patients and to effectively control the progress of glaucoma, the Glaucoma Group of Ophthalmology Branch of Chinese Medical Association has formulated this consensus after serious consideration and discussion. This evidence-based consensus puts forward suggestions on the characteristics, occurrence mechanism, risk factors, diagnosis, treatment, prevention and follow-up of ocular surface diseases associated with topical glaucoma medications.

The Integration of Diabetic Eye Screening into Hemodialysis Units in Northern Ireland.

Diabetes is rising globally and is the most common cause of both end-stage renal disease and blindness. People on hemodialysis have to attend several dialysis appointments per week, which can affect their attendance at diabetic eye screening. In addition, previous literature suggests patients on hemodialysis are more likely to have sight-threatening diabetic eye disease. This study aims to determine attendance at the Diabetic Eye Screening Program in Northern Ireland, diabetic retinopathy severity, and use of handheld retinal imaging in people with diabetes attending hemodialysis units in Northern Ireland. All patients with diabetes attending hemodialysis clinics regionally were screened and graded by the Diabetic Eye Screening Program in Northern Ireland using a handheld and/or conventional nonmydriatic fundus camera. All eligible people (N=149) were offered a Diabetic Eye Screening Program in Northern Ireland appointment, 132 attended, 34% of whom had not been seen in >3 years and 15% of whom had never attended the Diabetic Eye Screening Program in Northern Ireland despite multiple previous appointments. Altogether, 13% required urgent referral to hospital eye services, which is significantly higher than the national average of 0.4%. Those on hemodialysis are at high risk for sight-threatening diabetic retinopathy. Implementing the Diabetic Eye Screening Program in Northern Ireland in hemodialysis clinics enables timely diagnosis and referral.

Endotrophin as a Marker of Complications in a Type 2 Diabetes Cohort.

We investigated endotrophin, a profibrotic signaling molecule reflecting collagen VI formation, in serum and urine as risk marker for complications to type 2 diabetes. Endotrophin was measured in 774 individuals with type 2 diabetes. Outcomes included a composite kidney end point, first major adverse cardiovascular event (MACE), mortality, progression of albuminuria, incident heart failure, and sight-threatening eye disease. Adjusted Cox proportional hazards models were applied. Doubling of serum endotrophin was associated with the kidney end point (n = 49; hazard ratio 1.80 [95% CI 1.13-2.87]), first MACE (n = 66; 1.54 [1.04-2.28]), mortality (n = 156; 1.69 (1.31-2.19]), and incident heart failure (n = 42; 1.63 [1.02-2.60]). A doubling of urine endotrophin was associated with progression of albuminuria (n = 85; 1.20 [1.04-1.39]). Serum endotrophin was a risk marker for mortality and kidney and cardiovascular complications in type 2 diabetes. Urine endotrophin was a marker for albuminuria progression.

Insights into Current Management Strategies for Dysthyroid Optic Neuropathy: A Review.

Dysthyroid optic neuropathy (DON) is a potentially sight-threatening eye disease associated with Graves’ orbitopathy (GO). DON is not common in GO patients, reportedly occurring in only about 5% of patients. The pathogenesis of severe DON is considered to involve both muscular nerve strangulation and impaired blood flow. There is some objective grading of physical examination findings and the severity of GO, including a clinical activity score (CAS) and EUropean Group On Graves’ Orbitopathy (EUGOGO), but no specialized protocol completely characterizes DON. Most clinicians have decided that the combination of clinical activity findings, including visual acuity, color vision, and central critical fusion frequency, and radiological findings, including magnetic resonance imaging (MRI), can be used to diagnose DON. MRI has the most useful findings, with T2-weighted and fat-suppressed images using short-tau inversion recovery (STIR) sequences enabling detection of extraocular changes including muscle and/orbital fat tissue swelling and inflammation and, therefore, disease activity. The first-choice treatment for DON is intravenous administration of steroids, with or without radiotherapy. Unfortunately, refractoriness to this medical treatment may indicate the need for immediate orbital decompression within 2 weeks. Especially in the acute phase of DON, thyroid function is often unstable, and the surgeon must always assume the risk of general anesthesia and intra- and post-operative management. In addition, there are currently many possible therapeutic options, including molecular-targeted drugs. The early introduction and combination of these immunomodulators, including Janus kinase inhibitors and insulin-like growth factor-1 receptor antibody (teprotumumab), may be effective for GO with DON. However, this is still under investigation, and the number of case reports is small. It is possible that these options could reduce systemic adverse events due to unfocused glucocorticoid administration. The pathophysiology of DON is not yet fully understood, and further studies of its treatment and long-term visual function prognosis are needed.

Infectious Uveitis in Horses and New Insights in Its Leptospiral Biofilm-Related Pathogenesis.

Uveitis is a sight-threatening eye disease in equids known worldwide that leads to considerable pain and suffering. By far the most common type of uveitis in Germany and neighboring countries is classical equine recurrent uveitis (ERU), which is caused by chronic intraocular leptospiral infection and is the main cause of infectious uveitis in horses. Other infectious causes are extremely rare and are usually clinically distinguishable from ERU. ERU can be treated very effectively by vitreous cavity lavage (vitrectomy). For proper indications of this demanding surgery, it is necessary to differentiate ERU from other types of uveitis in which vitrectomy is not helpful. This can be conducted on the basis of anamnesis in combination with ophthalmologic findings and by aqueous humor examination. During vitrectomy, vitreous material is obtained. These vitreous samples have historically been used for numerous etiologic studies. In this way, a chronic intraocular leptospiral infection has been shown to be the cause of typical ERU and, among other findings, ERU has also been recognized as a biofilm infection, providing new insights into the pathogenesis of ERU and explaining some thus far unexplainable phenomena of ERU. ERU may not only have transmissible aspects to some types of uveitis in humans but may also serve as a model for a spontaneously occurring biofilm infection. Vitreous material obtained during therapeutically indicated vitrectomy can be used for further studies on in vivo biofilm formation, biofilm composition and possible therapeutic approaches.

Cluster of Symptomatic Graft-to-Host Transmission of Herpes Simplex Virus Type 1 in an Endothelial Keratoplasty Setting

PurposeDescemet's membrane endothelial keratoplasty (DMEK) is becoming the gold standard to treat corneal endothelial dysfunctions worldwide. Compared with conventional penetrating keratoplasty, infectious complications after DMEK are ill defined. We describe the clinical picture of 2 DMEK recipients, operated on the same day and in the same clinic, who developed atypical herpes simplex virus type 1 (HSV-1) infection in the transplant recipient eye within days post-DMEK. Because recipients received cornea tissue from 2 different donors prepared by the same eye bank, the likelihood of a common HSV-1 source was determined.DesignCase series.ParticipantsTwo DMEK recipients who developed atypical intraocular HSV-1 disease shortly after surgery and surplus cornea specimens of 6 donors.MethodsSurplus cornea donor (pre-DMEK cornea remnants and conditioned cornea storage and transport media) and recipient samples (post-DMEK aqueous humor) were assayed for HSV-1 DNA and infectious virus by real-time polymerase chain reaction (RT-PCR) and cell culture, respectively. Target-enriched whole viral genome sequencing was performed on HSV-1 DNA–positive ocular specimens.Main Outcome MeasuresClinical picture of atypical intraocular HSV-1 infection post-DMEK and presence and homology of HSV-1 genomes between ocular specimens of DMEK donors and recipients.ResultsHerpes simplex virus type 1 DNA was detected in aqueous humor and donor cornea specimens of both DMEK cases, but not in the cornea remnants of 6 randomly selected donors processed by the same eye bank. Infectious HSV-1 was isolated from the cornea remnant and corresponding culture medium of 1 cornea donor. Notably, whole-genome sequencing of virus DNA-positive specimens demonstrated exceptionally high genetic similarity between HSV-1 strains in recipient and donor specimens of both DMEK cases.ConclusionsData indicate cross-contamination of cornea grafts during DMEK preparation with subsequent graft-to-host HSV-1 transmission that caused atypical sight-threatening herpetic eye disease shortly after DMEK. Ophthalmologists should be aware that HSV-1 transmission by DMEK is possible and can lead to atypical ocular disease, a condition that can easily be prevented by taking appropriate technical and clinical measures at both eye bank and surgical levels.

A 'Real Life' Service Evaluation Model for Multidisciplinary Thyroid Eye Services.

Background/AimsThere is no universal consensus on the practical implementation and evaluation of the Amsterdam Declaration on Graves Orbitopathy in a Multidisciplinary Thyroid Eye Disease (MDTED) pathway. Recent recommendations from the UK TEAMeD-5 and BOPSS initiative highlight the importance of prevention, screening, and prompt referral of patients with moderate to severe and sight-threatening thyroid eye disease to multidisciplinary (MDTED) clinics and recommends annual auditing. We propose a practical service evaluation model with Key Performance Indicators (KPI) that are achievable and could be implemented across most TED pathways.Material and MethodsWe conducted a service evaluation from an integrated TED pathway in London with three MDTED clinics. Data was collected retrospectively from consecutive TED patients included: 1) Patient demographics, 2) Referral to first appointment time, 3) Documented smoking cessation and selenium supplementation advice, 4) Presenting disease activity and severity, 5) Investigations and treatments, including radio-iodine, 6) Time from decision to treatment initiation, 7) Initial and subsequent thyroid status.ResultsThe median age was 49.0 yrs, 77.5% (183/236) were female and 49.5% (101/204) Afro-Caribbean or Asian. At their first clinic attendance, 47.6% (110/231) were biochemically euthyroid and 76.7% (79/103) at discharge. All 23.1% (52/225) current smokers received smoking cessation advice and 64.8% (153/236) received selenium supplementation advice. Intravenous methylprednisolone was given to 33.9% (80/236) patients and 12.7% (30/236) received second-line immunosuppression. All 7.2% (17/236) patients with sight-threatening disease received treatment within two weeks of diagnosis.ConclusionsThis study forms a waymark for other units using TEAMeD-5 and BOPSS audit criteria. Dedicated electronic patient records with ongoing data capture, including quality of life assessments, and diagnostic coding would significantly aid future auditing, improve patient care, and facilitate a national audit of TED management. A future survey when the TED standards have become embedded would be instructive to see whether this has improved TED care.

Real-World Efficacy and Safety of Mycophenolate Mofetil in Active Moderate-to-Sight-Threatening Thyroid Eye Disease.

PurposeThere is no universal consensus on second-line agents for the treatment of moderate/severe to sight-threatening thyroid eye disease (TED) to maintain remission after first-line intravenous methylprednisolone (IVMP). This study investigates the efficacy and safety of mycophenolate mofetil (MMF) in TED patients in a real-world setting and over a longer period than previous randomized controlled trials.MethodsA retrospective cohort study of TED patients with active moderate/severe to sight-threatening TED seen over a 4-year period. Data collected were visual acuity (VA), Clinical Activity Score (CAS), Gorman Diplopia scores, MMF dosing and side effects at 24, 52 and 78 weeks. Clinical efficacy was defined as an absence of relapse: no decline in best corrected LogMAR VA, no need for further steroids, no increase in CAS of ≥2.ResultsOut of 23 patients, 20 patients were included in this study. 10% (2/20) stopped MMF before 24 weeks. Median duration of MMF treatment was 76 weeks (1–140 weeks). 55% (11/20) had dysthyroid optic neuropathy (DON). In those with active moderate-severe TED without DON, clinical efficacy was seen in 100% (8/8) at 24 weeks, 87.5% (7/8) at 52 weeks, and 83.3% (5/6) at 78 weeks, with CAS decreasing from a baseline of 2.78±1.99 to 0.50±0.58 at 24 weeks, 0.50±0.82 at 52 weeks and 1.00±1.30 at 78 weeks. In DON, improvements were seen in 90% (9/10) at 24 weeks, 100% (7/7) at 52 weeks and 100% (4/4) at 78 weeks, with significantly reduced CAS scores from 2.55±1.54 to 0.83±1.27, 1.00±1.17 and 0.63±0.95 at 24, 52 and 78 weeks, respectively. Gorman score, VA and soft tissue inflammation parameters also improved throughout. There were two significant side effects over the treatment period.ConclusionMMF appears to be an effective and safe second-line immunosuppressive agent. Further studies aimed at elucidating optimal dosing regimens and ideal treatment duration will prove helpful.

Bilateral exudative retinal detachment in HELLP syndrome, first description in North Africa: a case report

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a pregnancy disorder representing a severe form of preeclampsia and associated with high maternal and fetal mortality. Serous retinal detachment has been reported in eclampsia. However, bilateral exudative retinal detachment associated with HELLP syndrome has rarely been described. We report a case of a 32-year-old patient, gravida III para III, with hypertensive HELLP syndrome who developed bilateral exudative bullous retinal detachment following caesarean delivery at 33 weeks. A comprehensive management and a scheduled monitoring of this potentially sight-threatening eye disease led to saving useful vision.

Sight-Threatening Thyroid Eye Disease: Role of Diabetes Mellitus and Interaction with Other Risk Factors

The aim of the study was to investigate whether diabetes mellitus (DM) is an independent risk factor in sight-threatening thyroid eye disease (ST-TED) and explore the interaction of DM with other known risk factors in TED. This was a retrospective cohort study and included 202 consecutive TED patients presenting between 2013 and 2019. Data collected included demography, history of smoking, thyroid dysmetabolism, and presence of DM, TED-duration, activity and severity, best-corrected visual acuity (BCVA), and follow-up. Primary outcome measure was development of ST-TED and secondary outcome measures included change in BCVA, activity, and bilateral ST-TED. Mean age of the cohort was 52.14 + 9.14 years and 74 (36%) were male. DM was present in 49 (24%) and a positive history of smoking in 65 (32%) TED patients. Cox's proportional hazards showed the presence of DM (hazard ratio [HR] 2.22; P = 0.02) and a positive history of smoking (HR 3.62; P = 0.003) were significant risk factors for development of ST-TED and dysthyroid optic neuropathy (DON). Older age was a risk factor (HR 1.05; P = 0.02) for DON. DM increased the risk of developing bilateral ST-TED (OR 4.14; P = 0.004). Median follow-up was 4 months (range 0.1-96 months). A linear mixed model to predict longitudinal interaction between risk factors, found TED patients in DM group were likely to have worsening of visual function and a positive history of smoking accentuated this adverse outcome. DM and smoking are major independent risk factors predictive of ST-TED. Coexisting DM either singularly or in combination with smoking may predict worsening of visual function in TED patients.

Epidemiology of visual impairment, sight-threatening or treatment-requiring diabetic eye disease in children and young people in the UK: findings from DECS

BackgroundWe investigated the incidence and causes of sight-threatening diabetes-related eye disease in children living with diabetes in the UK, to inform the national eye screening programme and enable monitoring of...