Dupilumab induced ocular surface disease: A prospective case series.

PURPOSE: To identify the incidence, risk factors, demographics, and clinical profile of dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis (AD), propose a standardised treatment protocol (STP) and evaluate the response. METHODS: Prospective case series of AD patients treated in the Dermatology Department, Royal Victoria Infirmary, Newcastle upon Tyne, UK developing ocular symptoms after commencing Dupilumab between September 2018 and February 2020. A standard history and examination protocol were used including subjective symptom severity grading and Ocular Surface Disease Index (OSDI) questionnaire on each visit. Standard treatment was prescribed, and response evaluated. RESULTS: 32 of 113 included patients (28.31%) developed DIOSD, of which 20 (62.5%) were referred to the Cornea Service. Median age was 38.0 years (IQR 26.8; range 19-74). Male to female ratio was 1:1. Average time to onset of ocular symptoms from starting dupilumab was 9.2 weeks (IQR 8.8; range 0.1-40). 90% patients had bilateral conjunctival inflammation and blepharitis at presentation. Significant improvement in the subjective severity scale and the median OSDI score (from 34.0 to 10.2) was noted in response to topical eye treatment. Dupilumab was discontinued in none. CONCLUSIONS: DIOSD is not uncommon although, with timely referral and appropriate topical treatment better clinical outcome and patient satisfaction can be achieved without the need to discontinue Dupilumab. Prior allergic conjunctivitis did not affect the incidence or severity of DIOSD. Further prospective studies with longer follow-up and more focus on possible disease mechanism such as goblet cell related changes and immune response are needed.

Differences in minimal disease knowledge of keratoconus patients: results from an international survey.

BACKGROUND/AIMS: The objective of this multicentre, multinational, prospective study was to assess the level of basic understanding that individuals with keratoconus possessed about their condition. METHODS: We recruited 200 active keratoconus patients who were under regular review, and cornea specialists established a standard of 'minimal keratoconus knowledge' (MKK) that included an understanding of the definition, risk factors, symptoms and treatment options for the condition. We collected data from each participant regarding their clinical characteristics, highest level of education, (para)medical background and experiences with keratoconus within their social circle, and calculated the percentage of MKK attained by each patient. RESULTS: Our findings revealed that none of the participants met the MKK standard, with the average MKK score being 34.6% and ranging from 0.0% to 94.4%. Furthermore, our study showed that patients with a university degree, previous surgical intervention for keratoconus or affected parents had a higher MKK. However, age, gender, disease severity, paramedical knowledge, disease duration and best-corrected visual acuity did not significantly affect the MKK score. CONCLUSIONS: Our study demonstrates a concerning lack of basic disease knowledge among keratoconus patients in three different countries. The level of knowledge exhibited by our sample was only one-third of what cornea specialists would typically anticipate from patients. This highlights the need for greater education and awareness campaigns surrounding keratoconus. Further research is needed to determine the most efficient approaches for enhancing MKK and subsequently improving the management and treatment of keratoconus.

Minimally invasive corneal neurotization for neurotrophic keratopathy: The potential effect of age, denervation chronicity and lesion location.

Purpose: Neurotrophic keratopathy (NK) is an uncommon but challenging clinical condition characterized by altered corneal nerves and sensation leading to corneal damage. Corneal neurotization, a surgical technique that aims to "re-innervate" the cornea, has gained increasing popularity in view of the potential to permanently improve or even restore the normal corneal sensation. In this study, we aimed to report the outcomes of two cases of NK that underwent indirect minimally invasive corneal neurotization (MICN) with a sural nerve autograft, and to provide plausible explanations for the observed clinical outcomes. Observations: This was an interventional case series of two patients who underwent MICN for severe unilateral NK. The MICN technique was adapted from the technique originally described by Elbaz et al., in 2014. Clinical severity of NK was graded according to Mackie's grading system. Corneal sensation was measured using the Cochet-Bonnet esthesiometer (0-60mm) and corneal nerves were examined using in vivo confocal microscopy (IVCM) with Heidelberg HRT3 Rostock Corneal Module. Patient 1 was a 70-year-old man with a right grade III NK following trigeminal nerve decompression for trigeminal neuralgia. Patient 2 was a 62-year-old man with a left grade II NK following a left-sided acoustic neuroma resection. The denervation time was 23 years for both patients. Following the MICN surgery, none of the patients achieved sustained improvement in the corneal sensation (though patient 1 achieved a transient improvement in central corneal sensation to 20mm at 4 months' postoperative before returning to 0mm at 6 months' postoperative). IVCM did not reveal any changes in the corneal nerve density and morphology post-MICN. Conclusions and Importance: Based on our observations and the literature, we postulate that long denervation time, proximal injury to the trigeminal nerve and older patient age may serve as poor prognostic factors for MICN. As CN is being increasingly adopted in clinical practice for treating NK, understanding of these potential factors will facilitate better risk-benefit stratification and patient counselling. Future larger studies are required to elucidate these findings.

Long-Term Graft Survival and Decline in Endothelial Cell Density Following Penetrating Keratoplasty with Organ-Cultured Corneas.

INTRODUCTION: Endothelial cell density (ECD) changes long after penetrating keratoplasty (PKP) of organ-cultured corneas have been little studied. We aim to calculate the point when ECD decline stabilises following PKP with organ culture stored corneas. METHODS: This is an observational study of first-ever PKPs and first-ever re-grafts, performed over 17 years under a single surgeon. ECDs were acquired at 3 and 6 months, 1 year post-graft and annually thereafter by specular microscopy. Time-dependent ECD data was fitted to a log-biexponential model. RESULTS: We studied 465 first-ever grafts and 128 re-grafts. Mean recipient age was 59 years (range 0-96 years; SD 22). Median follow-up was 5.7 (range 0.2-17.1) years. Probability of ED at 5 years in first grafts and re-grafts was 4.4% (2.6-7.1%) and 14.8% (8.3-23.2%). In first grafts, ECD loss reached 0.6% per annum at 7.9 (6.2-9.6) years post-operatively. The half-lives of ECD loss during the immediate post-operative period for first grafts, re-grafts, dystrophies, ectasias, and previous ocular surgery are 20.1 (14.9-30.9), 12.8 (6.9-79.4), 19.5 (13.1-37.7), 26.2 (16.2-68), and 11.6 (6.7-41.3) months, respectively. The half-life during this rapid phase of ECD loss has an inverse correlation with graft survival at 10 years (r = - 0.89, p = 0.02). CONCLUSIONS: Rate of endothelial decompensation is higher in first grafts than re-grafts. ECD decline stabilises 7.9 years post-operatively in first grafts but then becomes lower than the physiological loss expected. Further work is needed to verify whether organ-cultured grafts reach physiological levels of ECD loss faster than hypothermically stored grafts.

Ocular manifestations of isolated corneal bee sting injury, management strategies, and clinical outcomes.

PURPOSE: The purpose of this study is to describe the presenting features, management strategies, and clinical outcome following bee sting injury to the cornea. METHODS: Retrospective case series involving 11 eyes of 11 patients with corneal bee sting injuries who presented over a period of 2 years. Nine of these 11 eyes had the presence of intact bee stinger in the cornea, which was removed immediately under an operating microscope and sent for microbiological and histopathological evaluation. The patients were managed as per the individual treatment protocol of the respective treating physicians. RESULTS: Six eyes (54.5%) had a good clinical outcome (best-corrected visual acuity [BCVA] >20/40) with medical therapy alone with no need for surgical intervention. Five eyes (45.5%) had a poor clinical outcome (BCVA <20/40) with medical therapy and required surgery; of which three required a combined penetrating keratoplasty with cataract surgery, while one required isolated cataract surgery and one underwent penetrating keratoplasty. Glaucoma was present in 3/5 eyes undergoing surgery, one of which required a trabeculectomy. Five of the six eyes who had a good clinical outcome with medical therapy alone had been treated with concomitant oral steroids, along with topical antibiotic-steroid combination therapy. CONCLUSION: Oral corticosteroid supplementation to the topical steroid antibiotic treatment in patients with corneal bee sting injury where corneal involvement and anterior reaction is severe at presentation or inflammation not ameliorating with topical steroids alone prevents serious vision-threatening complications such as corneal decompensation, cataract, and glaucoma.

Clinical and demographic study of microsporidial keratoconjunctivitis in South India: a 3-year study (2013-2015).

AIM: To study the demographic profile, clinical features, treatment outcome and ocular morbidity of smear-positive microsporidial keratoconjunctivitis. METHODS: Retrospective case series of all patients with clinical features of microsporidial keratoconjunctivitis and who were smear positive for the same on Gram stain from January 2013 to December 2015. Demographic data, predisposing factors, microbiological investigations, clinical course and visual outcome were analysed. RESULTS: Of the 10 655 patients with conjunctivitis, 550 (5.2%) patients were positive for microsporidia on Gram stain during this time period. The disease was prevalent throughout the year with an increased incidence from July to December. Bilateral involvement was seen in 27 (4.9%) patients. There was no predisposing risk factor in 428 (77.8%) patients. 384 (69.1%) patients had received prior treatment before presentation to us with the most common drug being antibiotic in 285 (49.4%) patients. All the patients underwent diagnostic corneal debridement and received topical 0.3% fluconazole eye drops four times a day. Of the 296 patients who followed-up, 187 (63.1%) patients had complete resolution without sequelae. 68 (22.9%) had persistent superficial punctate keratopathy, 30 (10.1%) developed subepithelial nummular keratitis. No significant change in visual acuity was seen in 255 (80.7%) eyes, two or more line improvement was seen in 48 (15.2%) eyes, while two or more line worsening was seen in 13 (4.1%) eyes. CONCLUSIONS: Microsporidial keratoconjunctivitis is prevalent in South India throughout the year. The characteristic clinical signs and simple microbiological investigation help us to differentiate it from adenoviral keratoconjunctivitis. The visual prognosis is good.

Microsporidial stromal keratitis masquerading as acute graft rejection.

PURPOSE: To describe the clinical features, disease course, management, and visual outcome of stromal microsporidial keratitis involving the corneal graft in an immunocompetent patient. METHODS: Case report. RESULTS: We report the case of a 21-year-old immunocompetent woman, who underwent penetrating keratoplasty for advanced keratoconus in her right eye and presented with features of acute graft rejection after 15 months. Standard treatment using topical and systemic steroids failed to reverse the graft rejection. A regraft was performed in that eye. Histopathology of the donor corneal button revealed microsporidiosis involving the deep stroma. CONCLUSIONS: Microsporidiosis is rarely encountered in a corneal graft and masquerades as acute graft rejection. Histopathology could help in making a final diagnosis.