Validation and Repeatability of the Epidermolysis Bullosa Eye Disease Index in Dystrophic Epidermolysis Bullosa.

PURPOSE: Dystrophic epidermolysis bullosa (DEB) is a devastating condition that causes painful corneal abrasions and vision loss. Epidermolysis Bullosa Eye Disease Index (EB-EDI) for the first time captures and quantifies EB-specific assessment of ocular symptoms and activities of daily living scales. This survey will become critical in developing new interventions on patients' quality of life. METHODS: Three-part set of the EB-EDI baseline, EB-EDI interval, and Ocular Surface Disease Index (OSDI) survey was distributed to 92 patients with DEB who previously reported eye symptoms on previous surveys. It was then posted online through several EB patient organizations. We compared the EB-EDI with the gold standard OSDI and examined the repeatability of the EB-EDI over a 7- to 15-day interval. RESULTS: Of the 45 individuals who initially responded, 30 of 45 (67%) completed the surveys sent 7 to 15 days later. The age of participants ranged from 6 to 51 years (mean 21 ± 15 years), and 60% (18 of 30) of participants were younger than 18 years. The overall Cronbach alpha values for the subscales of EB-EDI baseline and interval tools presented a good internal consistency (≥0.7). From 2 visits, the domain scores of EB-EDI baseline (0.94) and interval tools (0.83) were shown to have excellent test-retest reliability (intraclass correlation coefficient >0.8). By comparison, OSDI had the intraclass correlation coefficient score of 0.72 ± 0.11. The convergent validation analysis showed that correlations between the domain scores of EB-EDI baseline and interval tools and the subscales of the OSDI reached the hypothesized strength. CONCLUSIONS: Based on a 30-person repeated-measures study, we found that the EB-EDI has excellent reliability and validity specifically in patients with DEB.

Lemierre syndrome associated mycotic cavernous sinus thrombosis and carotid aneurysm after COVID-19.

Purpose: The purpose of this article is to report a case of Lemierre syndrome associated mycotic aneurysm of the intracavernous carotid artery leading to cavernous sinus syndrome in an otherwise healthy, young man in the setting of COVID-19 infection. Observations: An 18-year-old, otherwise healthy male athlete developed fever, chills, and headache and was found to be positive for COVID-19 with gram negative bacteremia. While on systemic antibiotic treatment, he developed acute, left-sided, 6th nerve palsy and was found to have bacterial sinusitis, left-sided intracavernous mycotic aneurysm, and cavernous sinus thrombosis on imaging studies. Despite systemic antibiotic and antiplatelet therapy, he developed progressively worsening left-sided ophthalmoplegia and vision decline. He subsequently underwent left internal carotid artery embolization and cervical internal carotid artery sacrifice with excellent outcome. Conclusion and importance: Lemierre syndrome can have atypical presentations and complications, including cavernous sinus thrombosis and mycotic aneurysms. Recognition of signs and symptoms, including progressive multiple cranial neuropathies, can aid in early diagnosis and management, which requires multidisciplinary care tailored to each individual based on risk of intervention.

Corneal Changes and Strategies to Improve Survival of Hypomorphic Collagen VII-Deficient Mice for the Study of Ocular Dystrophic Epidermolysis Bullosa.

Ophthalmic study of collagen CVII hypomorphic mice is uniquely challenging due to the strain's published survival rate to weaning of 24%. Because chronic ocular fibrosis requires time to develop, optimizing the survival rate is of critical importance. In this study, standard husbandry practices were enhanced by the addition of sterilized diet and drug delivery gels, acidified water, irradiated food pellets, cellulose fiber bedding, minimal handling, removal of siblings within 2-3 wk from birth, and a preferred housing location. Survival rates per breeding cycle, sex, weight, and cause of early euthanasia were recorded and analyzed over 43 mo. Overall, 49% of mice survived to weaning and 76% of weaned mice survived to 20 wk of age. Corneal opacities were seen in 65% of mice by 20 wk, but only 10% of eyes showed the sustained opacification that was indicative of fibrosis. Corneal opacities occurred at the same rate as in humans with epidermolysis bullosa. 66% of the mice showed weight loss at 11 wk. Males required early euthanasia 4 times more often than did females. Euthanasia was required for urinary obstruction due to penile prolapse in 88% of males. With our enhanced care protocol, hypomorphic mice in our colony survived at twice the published rate. With this revised husbandry standard, experiments planned with termination endpoints of 14 wk for males and 17 wk for females are more likely to reach completion.

Anterior-segment spectral domain optical coherence tomography in epidermolysis bullosa.

PURPOSE: Assess epidermolysis bullosa (EB)-related corneal pathology using anterior segment optical coherence tomography (AS-OCT) and correlate imaging with clinical metrics in EB patients versus age-matched controls. METHODS: EB patients and controls were recruited during an EB conference (July 2018) and at Tufts Medical Center (June-August 2019). Subjects completed a questionnaire, had best corrected visual acuity (BCVA) tested, and underwent AS-OCT scanning. Stromal and epithelial thickness were measured. Depth, length, and type of the three largest lesions were assessed by a masked examiner using a novel pathology grading system. Multivariate analysis of AS-OCT findings and clinical metrics was performed. RESULTS: 62 EB patients and 60 age-matched controls were enrolled. Mean BCVA was 1.8 lines worse in patients (p < 0.001). Vision loss was associated with increased stromal thickness. Discrete lesions were seen in 60.2% of patient eyes, averaging 1.71 ± 1.75 lesions in patients and 0.14 ± 0.42 in controls (p < 0.001). Mean primary lesion depth was 151.88 ± 97.49 µm in patients. Patients showed significant stromal thickening versus controls and lesions were most common in the periphery and inferiorly. Differences in frequency and duration of abrasions and severity of pain were all statistically and clinically significant in patients versus controls (p < 0.001). CONCLUSIONS: AS-OCT can visualize and quantify differences in the corneas of EB patients compared with age-matched controls. Novel findings include quantification of average depth, length, and severity of discrete lesions, and sparing of the superior quadrant from stromal thickening in EB patients. These results support use of AS-OCT and a questionnaire in clinical trials for new EB therapies.

Extended Wear Bandage Contact Lenses Decrease Pain and Preserve Vision in Patients with Epidermolysis Bullosa: Case Series and Review of Literature.

Purpose: To demonstrate the therapeutic benefit of extended wear bandage contact lens (BCL) use in patients with epidermolysis bullosa (EB) suffering from recurrent, painful, and slow-to-heal corneal epithelial defects.Methods: Case reports of three patients.Results: We report ophthalmic treatment of three pediatric patients, two with recessive dystrophic EB (RDEB) and one with junctional EB (JEB), who suffered frequently recurrent corneal abrasions and were treated with 30-day extended-wear bandage contact lenses (BCLs), replaced every month for at least 1 year. Pain and frequency of corneal abrasions improved immediately, and the BCLs were well tolerated. Vision was maintained or improved in all cases. Corneal ulcers did not occur while on antibiotic prophylaxis.Conclusions: Continuous and prolonged BCL therapy in patients with EB can be an effective way to immediately alleviate pain, prevent recurrent abrasions, and improve patient quality of life.

Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

BACKGROUND: Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The hypomorphic mouse model for DEB shows production of collagen VII at 10% of wild type levels in skin and spleen, but the eyes have not been described. Our purpose is to characterize the corneas to determine if this is an appropriate model for study of ocular therapeutics. METHODS: Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess presence and location of collagen VII protein within the hypomorphic mouse cornea. Additional IHC for inflammatory and fibrotic biomarkers transforming growth factor-beta-1 (TGF-ß1), alpha-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting corneal opacification were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. RESULTS: IHC and WB confirmed that hypomorphic mice produce less collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-ß1 showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. CONCLUSIONS: The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-ß1 appear to be the most consistent and strongest staining biomarkers in diseased mice. This mouse appears to mimic human corneal disease. It is an appropriate model for testing of therapeutics to treat EB ocular disease.

Retinal telangiectasis detected during a vision screening examination in a child with hearing loss led to the diagnosis of facioscapulohumeral muscular dystrophy.

A 2-year-old girl with congenital sensorineural hearing loss was found to have retinal exudation and subretinal fluid in her left eye. Further investigation revealed leaking retinal telangiectasias in her left eye and extensive areas of peripheral retinal nonperfusion in both eyes. A clinical diagnosis of facioscapulohumeral muscular dystrophy (FSHD) was confirmed by genetic testing. The patient was followed with serial intraoperative optical coherence tomography (OCT) scans, which demonstrated subretinal fluid in the macula and its subsequent resolution after treatment. She underwent 6 rounds of panretinal photocoagulation and 2 injections of intravitreal bevacizumab, which resolved the subretinal fluid and exudates.

Ocular misalignment in Graves disease may mimic that of superior oblique palsy.

BACKGROUND: The Parks-Bielschowsky three-step test (TST) can incorrectly indicate that a superior oblique muscle is paretic in patients with restrictive strabismus. Although this pitfall in diagnosis has been widely reported, no large studies have examined the incidence of a positive TST in patients with Graves disease. METHODS: We performed a retrospective chart review of 31 consecutive patients with Graves orbitopathy examined at Children's Hospital of Boston from 2003 to 2007. We analyzed ocular ductions, misalignment, and torsion, and thyroid function studies. RESULTS: Six (20%) of the patients had a positive TST, 3 (10%) of which showed excyclotorsion in at least one eye. However, of the 6 patients, 5 had obvious ocular adnexal signs of Graves disease and 2 had obvious supraduction deficits, leaving only 1 (3%) patient in whom the clinician would have mistakenly diagnosed a superior oblique palsy. CONCLUSIONS: Although a positive TST occurs frequently in Graves disease, other clinical features should allow distinction from superior oblique palsy in most patients.