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Archimedes LD Agahan1,3, Jenice Torres1, Graciana Fuentes-Páez1, Hernan Martínez-Osorio1, Antonio Orduña2, Margarita Calonge11Ocular Immunology and Uveitis Unit, Institute of Applied Ophthalmobiology (IOBA), 2Microbiology Department, University of Valladolid, Valladolid, Spain; 3Department of Ophthalmology and Visual Sciences, University of the Philippines, Philippine General Hospital, Manila, PhilippinesObjective: To report the clinical features and management of seven cases of intraocular inflammation caused by Rickettsia infection and review published literature.Methods: Rickettsia conorii or Rickettsia spp. infection was diagnosed based on the following criteria: (1) positive serology according to the European Guidelines, (2) titer normalization after specific treatment, and (3) complete resolution of ophthalmic disease and accompanying symptoms after antibiotic therapy.Results: Seven patients were referred for uveitis of unknown etiology. All came from regions where Mediterranean spotted fever is prevalent. One patient met the European guidelines criteria for Rickettsia spp. infection, while the other six cases met the criteria for R. conorii infection. The main symptoms were visual loss, floaters, eye redness, photophobia, and ocular pain. Predominant ophthalmic signs included vasculitis, choroiditis, vitritis, and macular edema. All patients required antibiotic treatment that resulted in the remission of the infection. Doxycycline was the first choice and the only antibiotic used to treat four patients. One patient needed ciprofloxacin as a second antibiotic after not responding to doxycycline. Two patients had doxycycline as a second antibiotic after not responding primarily to sulfonamides (which had been given after 2–3 days of doxycycline gastric intolerance); one of these patients needed ciprofloxacin as a third antibiotic.Conclusion: Intraocular inflammation can occur as the main manifestation of Rickettsia conorii or Rickettsia spp. infection. It should be considered as a differential diagnosis for uveitis especially for patients living in countries where this infection is endemic in the world. Antibiotic treatment remains effective in the management of Rickettsia infection.Keywords: intraocular inflammation, Mediterranean spotted fever, Rickettsia conorii, uveitis

Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in β cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of β cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to report visual, topographic, and satisfaction comparative results between symmetrical and asymmetrical presbyLASIK after 18 months., Methods: Longitudinal, comparative case series of hyperopic presbyopes who underwent presbyLASIK, in a private clinical setting. Monovision symmetrical (plano target both eyes) versus asymmetrical [dominant eye (DE) = plano target; nondominant eye (NDE) = -0.50 diopter (D) target]. Pre- and postoperative variables included monocular and binocular, distance and near, uncorrected visual acuity (VA), best corrected visual acuity, spherical equivalent, addition (Add), topography SimK (Km), and topographic astigmatism. Topographic central corneal power increase was measured 3 and 18 months postoperatively. Data were reported as mean, range, and standard deviation and analyzed with Student t-test (P < 0.05 for statistical significance) and Pearson correlation coefficients., Results: The symmetrical group consisted of 16 patients and the asymmetrical group of 14 patients, with a mean age of 53.5 ± 2.3 and 51.9 ± 2.5 years. Postoperative results, after 18 months, for symmetrical versus asymmetrical presbyLASIK were as follows: distance UCVA 0.8 ±0.20; 0.9 ± 0.2 (P < 0.01); near UCVA 0.9 ± 0.2; 0.8 ± 0.2 (P < 0.01); SE -0.20 ± 0.50; -0.3 ± 0.3D (P < 0.01); Add 0.5 ± 0.5; 0.9 ± 0.9 (P < 0.01); mean Km 44.8 ± 1 D; 43.9 ± 1.1 D (P < 0.01); mean central corneal power differential 1.4 ± 0.8 D; 1.7 ± 1.1 D (P < 0.01), respectively. Stability: -0.16 D, DE -0.13 D and NDE -0.16 D, and SE predictability -0.40; DE -0.28 D and NDE -0.53 D. Safety index 1.0; 1.0, efficacy distance VA 0.8; 0.9, and near VA 0.90; 0.8. More than 90% were within ±0.50 D of the intended target. Twenty eyes required enhancement, and results were not significantly different. Mean satisfaction (0-10 points) for symmetrical patients was 7.0 ± 2.6 and 7.3 ± 2.8 points for asymmetrical patients., Conclusions: Symmetrical and asymmetrical presbyLASIK significantly improved distance UCVA, near UCVA, after 18 months.

Purpose: To record visual and refractive data in eyes with previous radial keratotomy (RK) and corneal instability undergoing corneal cross-linking (CXL)., Methods: Case series of eyes with RK and refractive instability undergoing CXL with riboflavin and UV-A radiation. The following variables were recorded before 3 and 6 months after CXL: sphere, spherical equivalent (SE), uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), topographic astigmatism, mean topographic K (Km), pachymetry, and Q values., Results: Seven eyes of 4 patients with pre-CXL variables included mean sphere [-0.7 ± 3.2 diopters (D)], astigmatism (2.5 ± 1.17 D), SE (-2.1 ± 3.1 D), UCVA (0.3 ± 2.0), BSCVA (0.63 ± 0.36), Km (38.75 ± 5.74 D), pachymetry (522 ± 36.8 μm), and Q (1.73 ± 1.34). Three months after CXL, mean sphere was +1.0 ± 3.0 D (P = 0.00); astigmatism, 2.5 ± 1.2 D (P = 0.95); SE, 0.3 ± 2.2 D (P = 0.008); UCVA, 0.41 ± 2.7 (P = 0.22); BSCVA, 0.80 ± 0.27 (P = 0.14); Km, 37.5 ± 5.7 D (P = 0.3); pachymetry, 491 ± 33.74 μm (P = 0.00); and Q, 2.27 ± 1.8 (P = 0.22). Six months after CXL, mean sphere was 0.53 ± 3.5 D (P = 0.00); astigmatism, 1.62 ± 1.76 D (P = 0.13); SE, 0.52 ± 2.9 D (P = 0.023); UCVA, 0.60 ± 2.0 (P = 0.018); BSCVA, 0.9 ± 0.15 (P = 0.03); Km, 38.3 ± 4.10 D (P = 0.64); and Q, 1.7 ± 0.78 (P = 0.80)., Conclusions: Short-term follow-up of RK patients treated with CXL showed clinical and statistically significant improvement.

Purpose: To evaluate mRNA levels of the ocular mucins MUC1, MUC2, MUC4, MUC5AC, and MUC7 in conjunctival impression cytology samples from patients with moderate to severe dry eye syndrome (DES) compared with a population of healthy subjects; and to investigate the use of the levels of these mucin genes as biomarkers of DES and subsequently as a potential diagnostic test for DES., Methods: This prospective study commenced in the year 2000 and ended in the year 2009. Thirty-eight patients with DES and 43 age- and sex-matched healthy subjects completed the initial part of the study. Investigations were repeated at a later stage in 16 healthy subjects and 30 patients with DES, which were used as external validation data. Conjunctival impression cytology was performed in all subjects to test gene expression of ocular mucin genes MUC1, MUC2, MUC4, MUC5AC, and MUC7. Statistical analysis was performed to determine whether there was a difference in the levels of mucin gene expression between the two groups of subjects. Sensitivity and specificity of mucin gene expression for the diagnosis of DES was calculated., Results: Expressions of MUC1, MUC2, MUC4, and MUC5AC (P < 0.0001) were significantly lower in conjunctival epithelium of patients with DES compared with that in normal subjects. These results were replicated in the external control subject and patient groups. MUC1 expression levels demonstrated the greatest sensitivity (83.3%) and specificity (87.5%) among all genes tested., Conclusions: The data strongly suggest that the expression levels of MUC1 may be used as a diagnostic test in DES for investigational and selective clinical trials.

Purpose: To report 2 cases of keratopathy after uneventful cross-linking procedures for grade 3 keratoconus., Methods: Two patients (21 and 11 years old) with grade 3 keratoconus underwent uneventful cross-linking in 1 eye. In both patients, multiple peripheral stromal precipitates, which extended centripetally, were observed 48 hours after the procedure. Sample cultures were negative for bacteria, fungi, and parasites., Results: Cornea infiltrates slowly resolved after combined topical antibiotic/antifungal/povidone/steroids treatment. Final best spectacle-corrected visual acuity was 20/25 for patient 1, after uneventful bilateral toric intraocular contact lens (ICL) (Staar Surgical) implantation, but faint and paracentral scarring persisted. Final best-corrected visual acuity was 20/25 for patient 2 with gas-permeable contact lens wear, despite stromal scarring., Conclusions: Cross-linking associated with sterile keratitis is an unusual entity of unknown etiology, which can lead to stromal scarring.

Purpose: To report a case of a 5-year-old child with CHARGE association and bilateral conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma treated with topical interferon-alpha., Methods: Case report., Results: A 5-year-old girl, diagnosed with nonclassical CHARGE association and hyper-immunoglobulin M (IgM) syndrome, was referred with a 2-month history of suspected purulent bilateral streptococcal conjunctivitis. Clinical symptoms did not resolve despite multiple antibiotic treatments, and her clinical course was attributed to underlying immunodeficiency. Biomicroscopy showed salmon-colored, nodular lesions occupying both fornices and caruncles. Inferior conjunctival biopsy was performed, and MALT lymphoma was diagnosed. Bilateral treatment was initiated with topical interferon-alpha, applied 3 times a day at a concentration of 5 x 10 U/m/d, for 4 months. Complete regression of symptoms and conjunctival lesions was achieved. No recurrences have been observed after 1-year follow-up., Conclusions: We report the use of topical interferon-alpha as treatment for bilateral conjunctival MALT lymphoma in a young child with CHARGE association and hyper-IgM syndrome.

We report a 29-year-old white female with conjunctival pigmentation after a Stevens-Johnson syndrome (SJS) episode triggered by sulfasalazine. The patient developed bilateral tarsal and forniceal conjunctiva and black pigmentation. Diagnostic biopsy showed stromal monocyte infiltration consistent with chronic phase SJS and conjunctival pigment of melanic origin and not due to drug deposition. Treatment with topical steroids and unpreserved artificial tears resulted in improvement of clinical symptoms; however, pigmentation was unchanged after 2 years.

Background and Aims: We report a case of subretinal fibrosis and panuveitis syndrome as an extraintestinal manifestation of ulcerative colitis., Materials and Methods: We present an interventional case report of a 40-year-old female patient with inactive ulcerative colitis referred to our center for refractory uveitis in her right eye., Results/findings: She was diagnosed with subretinal fibrosis and uveitis syndrome after work-up ruled out tuberculosis, bartonellosis, Lyme disease, and sarcoidosis. Right eye multifocal choroiditis and panuveitis syndrome with subretinal fibrosis was diagnosed, and posterior pole subretinal fibrosis caused a 90% loss of visual efficiency. She had concurrent dermatological manifestations but no gastrointestinal symptoms. One year of immunosuppressive therapy with methotrexate (7.5 mg/week) controlled ocular inflammation. Two colitis episodes, with no visual involvement, were recorded during follow-up. Her final, right-eye, best-corrected visual acuity remained stable at 0.160 due to scarring sequela after 7 years of follow-up., Interpretation/conclusion: Subretinal fibrosis and uveitis syndrome can occur as a sight-threatening extraintestinal manifestation of ulcerative colitis.