Histiocytosis and adult-onset orbital xanthogranuloma in 2023: a review of the literature and mini case series.

PURPOSE: Within the large umbrella of histiocytosis are a few similar yet heterogenous entities involving the orbit and periocular tissues with or without systemic infiltration, termed adult onset xanthogranuloma or orbital xanthogranuloma. Due to rarity of these conditions, different classifications in use, diverse clinical presentations and still unknown etiology, the aim of this paper was to provide an up-to-date literature review of the actual understanding of histiocytosis and its subgroups involving the orbit and periocular area, diagnostic strategies and therapeutic modalities. METHODS: We present a review of literature and small case series comprising four patients diagnosed and treated in the period from 2001 until 2023 in our hospital. Clinical files of 4 patients with adult-onset xanthogranulomatous disease of the orbit and ocular adnexa (AOXGD) were reviewed retrospectively. Clinical, laboratory, radiological, histopathological, and immunohistochemical findings were reexamined. RESULTS: Reviewing medical records of our patients with AOXGD, we found significant overlap between histiocytosis and different immune disorders. A broad workup should be considered in these patients as they can harbour severe immune disfunctions and hematologic disorders. Preferred treatment modality depends on a histopathologic type of AOXGD, clinical presentation and systemic involvement and should be conducted multidisciplinary. CONCLUSION: The diagnosis is often delayed because of its rarity and diverse clinical findings. Development of molecular genetic tests, detection of BRAF V600E mutation and different types of kinase mutations, mutations in transcriptional regulatory genes as well as tyrosine kinase receptors have shed a new light on the etiopathogenesis and potential targeted treatment of histiocytosis.

Nonsurgical treatment for upper eyelid retraction in patients with inactive Graves' orbitopathy.

PURPOSE: To evaluate the effectiveness of incobotulinumtoxinA (Xeomin®) in treating upper eyelid retraction in patients with Graves orbitopathy (GO) initially scheduled for surgery via two different application sites. METHODS: This is a comparative, prospective study, conducted at the Department of Ophthalmology, Medical School, University Hospital Centre Zagreb, EUGOGO site (EUropean Group On Graves' Orbitopathy) in Croatia from January 2020 till January of 2021 in accordance with national health headquarter recommendations. All patients were classified as inactive with marked eyelid retraction and randomly divided into groups according to application sites. Group A underwent transconjunctival application (18 eyes) and group B transcutaneous application (20 eyes) of incobotulinumtoxinA. The primary end point of this study was lowering the eyelid, to alleviate anterior eye segment symptoms and achieve acceptable aesthetic appearance until surgery becomes available. RESULTS: There were no nonresponders and we found no statistically significant difference in the degree of lowering the eyelid between the two application sites. Following rules for avoiding spread of SARS-CoV-19, none of the patients included in this study were infected. Moreover, participants reported diminishing of anterior eye segment irritation and improved aesthetics. CONCLUSION: Treatment of inactive GO patients with incobotulinumtoxinA for upper eyelid retraction is efficient and safe and can be used as an adjuvant treatment while patients wait for surgery, by alleviating symptoms and improving the level of aesthetic satisfaction without causing a threat to anterior eye segment and visual function. The study showed that effect of treatment was the same, whether we applied the toxin transconjunctivaly or transcutaneously.

The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs euthyreosis.

PURPOSE: Simultaneous analyses of the contents and ratios of 12 cytokines and growth factors in single samples of human tears were performed, and the results were compared between a group of healthy subjects and a group of patients with Graves' hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO). METHODS: Determinations and concentration measurements of interleukins (IL-2, IL4, IL-6, IL-8, IL-10, IL-1α, and IL-1ß) interferon (IFN-γ), tumor necrosis factor (TNF-α), monocyte chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were performed with single tear samples from 21 patients with hyperthyreosis and 22 healthy subjects. The analyses were performed using a Randox microchip with an Evidence Biochip Array Analyzer. RESULTS: We found significant differences between the healthy donor group and the hyperthyreosis group in the levels of IL-6, IL-10, VEGF, IL-1α, and MCP-1. The concentration of IL-6 was considerably higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group, and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN-γ levels were higher in the hyperthyreosis group. The ratios of all of the cytokines to anti-inflammatory IL-10 were significantly elevated in the hyperthyreosis group. CONCLUSION: There are clear differences in the levels of cytokines and growth factors in the tears of healthy subjects and patients with GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome (DTS) could be an early sign of occult TAO in Graves' hyperthyreosis patients.

Quality of Life and Depression Level in Patients with Watery Eye.

BACKGROUND: The aim of this study was to assess subjective, human aspect of the medical condition, evaluate the quality of life (QOL) and level of depressive symptoms in patients with watery eye and compare it with patients with two most common causes of visual deterioration: cataract and macular region pathology. The results of this study may serve to raise awareness of watery eye impact on a large number of patients and subsequently promote their treatment in order to restore full visual and life quality necessary for normal human functioning. SUBJECTS AND METHODS: In this prospective, randomised, questionnaire-based study, we have surveyed three groups of patients with a total of 210 patients: group with the watery eye of different etiology (n=69), group with one pseudophakic eye and one cataract eye (n=73) and group with the unilateral pathology of the macular region (n=68). All three groups underwent a complete ophthalmologic examination. To examine the overall quality of life we have used a modified vision-related quality of life questionnaire (VR-QOL) and to evaluate depression level "Beck Depression Inventory - 2". The results were analyzed with statistical program STATISTICA 13. RESULTS: Compared to group with unilateral cataract eye and to group with unilateral pathology of the macular region, the results of this study show that patients with watery eye have significantly decreased quality of life in all daily activities, particularly in outdoor activities (F=125.80, df=2/143, p<0.01), during sports (F=36.67, df=2/143, p<0.01) and interpersonal relations (F=18.73, df=2/143, p<0.01). Results between three groups showed that group with watering eye expressed highest depression level and group with one pseudophakic eye and the other cataract eye the lowest (F=25.86, df=2/207, p<0.01). CONCLUSION: Watery eye has a significant impact on vision-related quality of life. Our research showed that patients with watery eye had expressed more depressive symptoms than other groups, but still without statistically significant value. Since it affects a large and heterogenic group of patients it is important to be recognized on time and treated etiologically in attempt to restore full function and life quality. The results of this study may serve to raise awareness of watery eye impact on a large number of patients and subsequently promote their treatment in order to restore full visual and life quality necessary for normal functioning.

Changes of Drusen Number and Central Retinal Thickness in Age-Related Macular Degeneration Patients Over Two Years

Age-related macular degeneration (ARMD) is the leading cause of blindness in developed world but there are still much unknown facts about the disease itself. Age, genetic factors and smoking are the three main risk factors for the development of ARMD, but the exact pathophysiological mechanism of the disease remains unknown. Current high resolution optical coherence tomography devices provide ample new information on retinal layers, drusen characteristics and their interaction. In this study, we analyzed 44 eyes with drusiform dry ARMD using high resolution optical coherence tomography over a 2-year period. Our results showed a statistically significant increase in drusen number in both females and males in the 2-year period. On average, increment by 4 and 5 drusen per eye during the 2-year period was recorded in female and male patients with drusiform dry ARMD, respectively. Also, statistical analysis of the central retinal thickness showed that women with drusiform dry ARMD had a statistically significantly thinner macula than their male counterparts.

Pseudovitelliform maculopathy associated with hereditary hemochromatosis.

Background: Hereditary hemochromatosis (HH) is an inherited autosomal recessive iron metabolism disorder resulting from a C282Y mutation in the HFE gene. Mutations in the HFE gene may result in iron accumulation and oxidative stress in the retina, resulting in macular degeneration. This article describes two patients with HH who were treated with erythrocytapheresis or phlebotomy, with no exposure to deferoxamine or any other chelation therapy, and who developed visual symptoms. Case Presentation: Both patients had known diagnoses of HH. Because of visual symptoms, they were referred to the ophthalmology clinic and underwent a retinal exam, multimodal imaging, and electrodiagnostic studies, which revealed structural and functional degeneration of the central macula. Fundus photography, fluorescein angiography, and fundus autofluorescence revealed changes at the level of the retinal pigment epithelium (RPE) in the central macula. In addition, optical coherence tomography revealed subfoveal accumulation of hyperreflective material at and below the RPE. Multifocal electroretinography confirmed a decreased cone response, whereas the full-field electroretinogram was unremarkable. Genetic testing ruled out Best's vitelliform macular dystrophy and the other known hereditary macular dystrophies. The patients had known diagnoses of HH, homozygous C282Y mutations in the HFE gene, and no comorbidities; thus, we presumed that HH led to the observed morphological and functional disorders of the RPE, which in turn caused structural macular changes in both patients. Conclusions: Considering the macular findings and the nature of the patients' primary illness, we believe that the accumulation of iron and photoreceptor metabolic products caused dysfunction in the RPE, which led to morphological and functional changes in the macula. Because the patients were not treated using chelating agents, we attribute the macular changes solely to iron accumulation and oxidative stress caused by the pathophysiological processes of HH. Further studies are needed to identify the plausible molecular or cellular insults underlying pseudovitelliform macular degeneration in patients with HH.

Influence of Clinically Active Graves' Ophthalmopathy on Spherical Equivalent and Visual Acuity.

Purpose: Clinical experience regarding the fluctuations of the refractive error of the eye during the different stages of Graves' ophthalmopathy observed through outpatient clinic frequent check-ups points towards an underestimated and often overlooked problem. Published data about it are sparse. The clinical manifestations of Graves' ophthalmopathy can be understood from the perspective of "compartment syndrome" and literature implies how such changes can affect the refractive error and consequently, the visual acuity. The purpose of the study was to explore how the clinical activity score of Graves' ophthalmopathy affects refractive error and visual acuity. Patients and Methods: The study was prospective and observational, including 60 eyes of 30 patients with clinically active Graves' ophthalmopathy. All the patients were monitored and evaluated over a period of 36 months by the clinical activity score, spherical equivalent and visual acuity. All the observed parameters were statistically analyzed. Results: The mean values of spherical equivalent and visual acuity throughout the observed period showed continuous fluctuation. Repeated measure analysis of variance showed statistically significant differences in visual acuity and spherical equivalent over the observed period. There was a statistically significant positive correlation between visual acuity and clinical activity score. The correlation between spherical equivalent and clinical activity score was also positive but not statistically significant. Conclusion: A decrease in the clinical activity score is either the result of a spontaneously resolving course of Graves' ophthalmopathy or a consequence of treatment, so lowering in fluctuation of refractive error and improved visual acuity may be associated with a reduction in orbital inflammation.

Common variant in myocilin gene is associated with high myopia in isolated population of Korcula Island, Croatia.

AIM: To study the association between genetic variants in myocilin and collagen type I alpha 1 genes and high myopia in an isolated island population. METHODS: A total of 944 examinees from the genetic epidemiology study conducted on the island of Korcula, Croatia, were included in the study. We selected 2 short nucleotide polymorphisms (SNP) available in our genome-wide scan set of SNPs that were previously associated with high myopia and used them to replicate previous claims of possible association. RESULTS: Nineteen cases of high myopia, defined as the refraction of

Superior Ophthalmic Vein Thrombosis with Complete Loss of Vision as a Complication of Autoimmune and Infective Conditions.

PURPOSE: To present our experience in the management of superior ophthalmic vein thrombosis (SOVT), which is a rare, but extremely serious condition if not recognized and managed promptly and appropriately. METHODS: Two patients with septic and aseptic SOVT are presented. Clinical characteristics, radiographic features, management techniques, and outcomes are described. RESULTS: In the first case thrombosis occurred as a complication of functional endoscopic sinus surgery. In the second case thrombosis occurred as a complication of untreated inflammatory bowel disease: ulcerative colitis. Both cases resulted with permanent unilateral blindness. CONCLUSION: SOVT is a rare entity. There are no guidelines, just recommendations for disease management. Based on our experience, broad-spectrum intravenous antibiotic, anticoagulation, and steroid therapy should be promptly introduced and if needed surgical intervention. SOVT can lead to devastating complications which include permanent loss of vision and in some cases a fatal outcome.

Ocular findings in patients with chronic renal failure undergoing haemodialysis.

The aim of this paper was to evaluate the ocular findings in patients with chronic renal failure (CRF) undergoing haemodialysis (HD). In 64 patients undergoing haemodialysis (30 female and 34 male), aged 24-83 years (mean 58 years) on haemodialysis 1-213 months (mean 47 months) complete ocular examination were performed: visual acuity (VA), intraocular pressure (IOP), biomicroscopic examination and fundoscopy. On right eye sixty-nine percent of patents had VA 0.6 or better, and on left eye 84% of patients had VA 0.6 or better. Mean IOP before dialysis was 15 mmHg and after dialysis was 14 mmHg. In 9 patients (14%) we found corneo-conjunctival calcium deposits. No correlation of ocular calcification and parathyroid hormone (PTH) level or calcium and phosphate product were observed. 39 (60%) patients had cataract. Hypertensive vascular changes were seen in 44 (68%) patients and in 6 (7%) patients age-related macular degeneration. Seven patients had diabetes mellitus and in 5 diabetic retinopathy was observed. Patients with CRF or who are receiving HD represent unique group of patients. Pathologic change could be found in many tissue and organs, therefore we suggest ocular examination more frequently in dialysis patients.

Intralesional triamcinolone acetonide injection for chalazion.

The aim of the study was to evaluate the efficacy of intralesional triamcinolone acetonide injection in primary and recurrent chalazion. The study included 30 patients with primary and recurrent chalazion (37 cases) and 24 patients as a control group. Patients with primary and recurrent chalazion received intralesional injection of 0.1 to 0.2 mL triamcinolone acetonide (40 mg/mL). Control group received intralesional injection of 0.1 to 0.2 mL 0.9% NaCl. Data on the lesion size, including digital color photography, lesion regression or recurrence, and complete ophthalmic examination were recorded at the time of injection and after a week or two until resolution or surgical excision. Success was defined as at least 80% decrease in size with no recurrence. Resolution of the lesion was found in 35 cases after one or two injections, with a mean time to resolution of 15.27 +/- 6.12 days. Subcutaneous injection of the steroid triamcinolone acetonide in primary and recurrent chalazion appears to be a simple and efficacious therapeutic option for chalazion.