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Background: Warburg-Cinotti syndrome is a rare syndrome caused by de novo or inherited variants in discoding domain receptor tyrosine kinase 2 (DDR2). Only six cases have been reported worldwide and our knowledge of this disease remained sparse especially from an ophthalmological perspective, since previous literature mostly focused on systemic malformations or genetics., Case Presentation: A seven-year-old boy developed a gelatinous vascularized conjunctiva-like mass secondary to trauma. The mass enlarged and gradually invaded the cornea. With each surgical intervention, the mass recurred and grew even larger rapidly. The patient ended up with the mass covering the entire cornea along with symblepharon formation. Whole exome sequencing revealed a hemizygous variant in the DDR2 gene, which is consistent with Warburg-Cinotti syndrome., Conclusions: Considering Warburg-Cinotti syndrome, we should be vigilant of patients exhibiting progressive conjunctival invasion of the cornea, even those without systemic manifestations or a positive family history., (© 2024. The Author(s).)

Purpose: To investigate the molecular mechanism of pathological keratinization in the chronic phase of ocular surface (OS) diseases., Methods: In this study, a comprehensive gene expression analysis was performed using oligonucleotide microarrays on OS epithelial cells obtained from three patients with pathological keratinization (Stevens-Johnson syndrome [n = 1 patient], ocular cicatricial pemphigoid [n = 1 patient], and anterior staphyloma [n = 1 patient]). The controls were three patients with conjunctivochalasis. The expression in some transcripts was confirmed using quantitative real-time PCR., Results: Compared to the controls, 3118 genes were significantly upregulated by a factor of 2 or more than one-half in the pathological keratinized epithelial cells (analysis of variance P < 0.05). Genes involved in keratinization, lipid metabolism, and oxidoreductase were upregulated, while genes involved in cellular response, as well as known transcription factors (TFs), were downregulated. Those genes were further analyzed with respect to TFs and retinoic acid (RA) through gene ontology analysis and known reports. The expression of TFs MYBL2, FOXM1, and SREBF2, was upregulated, and the TF ELF3 was significantly downregulated. The expression of AKR1B15, RDH12, and CRABP2 (i.e., genes related to RA, which is known to suppress keratinization) was increased more than twentyfold, whereas the expression of genes RARB and RARRES3 was decreased by 1/50. CRABP2, RARB, and RARRES3 expression changes were also confirmed by qRT-PCR., Conclusions: In pathological keratinized ocular surfaces, common transcript changes, including abnormalities in vitamin A metabolism, are involved in the mechanism of pathological keratinization.

Objective: The aim of this study was to describe the clinical, confocal microscopic, histologic, and virologic features of horses with macrodendritic ulcerative keratitis and conjunctival lymphoid hyperplasia associated with equine herpesvirus-2 and equine herpesvirus-5 infection., Animal Studied: Four foals with bilateral ocular disease., Procedures: Complete ophthalmic examination was performed for each horse, and corneal samples were collected for cytology and microbiologic evaluation, including virus isolation and molecular diagnostics for the equine herpesviruses. In vivo confocal microscopy examination of the cornea was performed in two horses. Conjunctival biopsies for histopathology were collected from two horses with nodular conjunctival thickening., Results: Each horse had bilateral, large, superficial dendritic corneal ulcerations that covered extensive regions of the corneal surface. Corneal in vivo confocal microscopy examination in two horses detected inflammatory cells and populations of morphologically abnormal corneal epithelial cells adjacent to the ulcerations. The abnormal epithelial cells included round, relatively small, hyperreflective cells intermixed with elongated, enlarged, hyperreflective cells. Equine herpesvirus-2 was isolated from corneal samples of 2 horses and detected by PCR assay in the other two horses. Equine herpesvirus-5 was also detected by PCR assay in three of the horses. Conjunctival histopathology identified predominantly lymphocytic infiltrates. The macrodendrites and conjunctival masses resolved with topical antiviral therapy (cidofovir or idoxuridine) in all horses and did not recur., Conclusions and Clinical Relevance: The equine gammaherpesviruses may be associated with the development of macrodendritic ulcerative keratitis and conjunctival lymphocytic masses in foals. In vivo confocal microscopy of horses with macrodendrites revealed similar findings to other host species with herpetic dendritic keratitis., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Purpose: The aim of this study was to observe the expression of interleukin (IL)-17 and intercellular adhesion molecule (ICAM)-1 in conjunctivochalasis (CCH) and to analyze the correlations between cytokines and the severity of CCH., Methods: Serum samples were collected from 22 patients with CCH and 18 normal controls (NCs). The Ocular Surface Disease Index, tear film break-up time, Schirmer I test, and corneal fluorescein staining were used to evaluate the ocular surface signs and symptoms. The concentrations of IL-17, IL-23, and ICAM-1 in serum and cellular supernatants were measured by enzyme-linked immunosorbent assays, and the gene expression levels of cytokines were measured by a quantitative real-time polymerase chain reaction. The relationships between serum concentrations of IL-17, IL-23, and ICAM-1 with clinical ocular surface parameters in CCH were analyzed using the Spearman correlation analysis., Results: The concentrations of IL-17 and ICAM-1 in serum and cellular supernatants of CCH were significantly higher than those of NCs (all P < 0.001). The concentrations of IL-23 in serum and cellular supernatants of CCH showed no significant difference from those of NCs ( P > 0.05). The mRNA expression levels of IL-17 and ICAM-1 in conjunctival fibroblasts of CCH were significantly higher than those of NCs (all P < 0.001). The mRNA expression of IL-23 in conjunctival fibroblasts of CCH was higher than that of NCs, without a significant difference ( P > 0.05). Furthermore, the serum concentrations of IL-17 and ICAM-1 were positively correlated with Ocular Surface Disease Index and fluorescein staining (all P < 0.05), and negatively correlated with break-up time and Schirmer I test of CCH (all P < 0.05)., Conclusions: The expression levels of IL-17 and ICAM-1 were significantly increased in CCH serum and associated with the disease severity. We postulate that IL-17 and ICAM-1 may play a role in the pathogenesis of CCH. IL-17 and ICAM-1 antagonists may be a potential treatment option for CCH in the future., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Conjunctivochalasis is a degenerative condition of the conjunctiva that disrupts tear distribution and causes irritation. Thermoreduction of the redundant conjunctiva is required if symptoms are not relieved with medical therapy. Near-infrared laser treatment is a more controlled method to shrink the conjunctiva than thermocautery. This study compared tissue shrinkage, histology, and postoperative inflammation in thermoconjunctivoplasty performed on the mouse conjunctiva using either thermocautery or pulsed 1460 nm near-infrared laser irradiation. Three sets of experiments were performed on female C57BL/6J mice ( n = 72, 26 per treatment group and 20 control) to assess conjunctival shrinkage, wound histology, and inflammation 3 and 10 days after treatment. Both treatments effectively shrunk the conjunctiva, but thermocautery caused greater epithelial damage. Thermocautery caused greater infiltration of neutrophils on day 3 and neutrophils and CD11b + myeloid cells on day 10. The thermocautery group had significantly higher conjunctival expression of IL-1β on day 3. Expression of chemokine CCL2 was higher in the conjunctiva on day 3 and tear concentrations were higher on day 7 in the laser group. These results suggest that pulsed laser treatment causes less tissue damage and postoperative inflammation than thermocautery while effectively addressing conjunctivochalasis.

An 18-year-old female patient was referred with complaints of tearing and redness in the left eye for 3 months after a mild ocular trauma with a turkey feather. She was treated with topical antibiotics and corticosteroids with no improvement. Slit-lamp examination of the left eye showed a vascularized lesion with a polypoidal appearance due to multiple contiguous micronodules on the temporal and inferior bulbar conjunctiva. Results of the anterior and posterior segment examination were unremarkable in both eyes. A biopsy specimen of the conjunctival mass showed multiple tuberculoid granulomas composed of epithelioid histiocytes with associated Langhan's type multinucleate giant cells and a necrotic nodule surrounded by histiocytes and giant cells. The Mantoux test was positive with induration of 15mm. The patient was prescribed antituberculosis therapy. Three months after treatment initiation, the conjunctival lesions had resolved. Mycobacterium tuberculosis should be considered in cases of unilateral chronic recalcitrant conjunctivitis. Biopsy of a conjunctival mass is of utmost importance to establish a definite diagnosis., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Purpose: The purpose of this retrospective case series was to compare the outcomes of different treatment options for patients diagnosed with hereditary benign intraepithelial dyskeratosis (HBID)., Methods: The study is designed as a single-institution retrospective chart review of patients who were clinically diagnosed with HBID during their care at the Duke Eye Center. Patient demographics were obtained, and disease course after different therapies was analyzed., Results: Seventeen patients were diagnosed with HBID. 52.9% (9/17) of patients identified with HBID reported Native American ancestry. Medical therapy alone failed to reduce the size or number of corneal lesions in any patient identified in this study. Ten of the 17 patients required surgical intervention. Two eyes received corneal biopsies, 3 eyes received a full conjunctival lesion excision with amniotic membrane grafting, 12 eyes received superficial keratectomy with amniotic membrane grafting, and 1 eye received keratoprosthesis. Lesion recurrence was seen in 9 of the 10 patients treated with surgical excision with an average time to recurrence of 1.5 and 2 months for conjunctival excisions and superficial keratectomy, respectively, when excluding patients who missed scheduled postoperative follow-up appointments., Conclusions: Hereditary benign intraepithelial dyskeratosis is a rare and poorly understood disorder that predominantly affects people with Native American ancestry. Medical therapy only provides symptomatic relief, and patients who receive surgical excision almost always develop recurrence. As a result, we recommend future investigations focus on identifying the optimal surgical technique and timing to limit the morbidity of HBID and improve outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the clinical presentation, anatomical location, and histological features of congenital conjunctival cysts of the orbit. The location and the histological features of inflammation in these patients were compared with those for 293 orbital dermoid cysts., Patients and Methods: Retrospective review of the clinical details, imaging, and histopathology for patients who had excision of conjunctival cysts from their orbit between 1992 and 2020; patients with a history of trauma or surgery were omitted., Results: Twelve patients (7 male; 58%) with congenital conjunctival cysts were identified, the patients presenting at an average age of 16 years (median 26; range 1-61) with a symptoms for a mean duration of 20 months (median 24; range 6-36). The commonest symptoms were peribulbar lump (6/12 patients; 50%), and eyelid swelling and blepharoptosis (6/12 patients; 50%). An orbitaxl mass was palpable in 10 patients (83%), 3 patients (25%) had mild proptosis (1-3 mm), and the cysts were most commonly located superiorly (6/12 patients; 50%) or superonasally (3/12; 25%) in the anterior half of the orbit. Imaging was performed in 7 cases, this showing an intimate relation to the common sheath of the superior rectus/levator complex in 3 patients (25%) and to the trochlea in 1 (8%). All cysts were excised completely, and no patient had postoperative complications or recurrence. Chronic mild and nonspecific inflammation was evident within the cyst wall in 7 cases (54%), but-unlike 55% of the 293 dermoid cysts-none showed granuloma formation., Conclusion: Congenital conjunctival cysts are rare and usually present with a palpable mass in the upper eyelid sulcus. A significant proportion of these cysts have an intimate relationship with the trochlea, or the superior rectus, levator palpebrae or superior oblique muscles and, to minimize the risk of postoperative diplopia or ptosis, particular care must be exercised during surgery., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: The purpose of this article was to describe a modification to the traditional Gundersen flap technique that expands eligible eyes to include those with severe conjunctival scarring and to report results from a clinical case., Methods: A 68-year-old woman with a history of herpes simplex keratitis, multiple failed penetrating keratoplasties, lagophthalmos, persistent epithelial defect, and low visual potential in the left eye presented for the evaluation of a Gundersen flap. Severe superior bulbar conjunctival scarring precluded a traditional approach. A modified Gundersen flap technique using a contiguous flap of inferior palpebral-bulbar conjunctiva extending from the inferior tarsal border to the limbus was devised and performed., Results: The modified Gundersen flap technique successfully stabilized the ocular surface, obviating the need for a cosmetically disfiguring permanent tarsorrhaphy or an evisceration., Conclusions: This modified Gundersen flap technique expands the indications to eyes with severe conjunctival scarring and can be offered in eyes with previous trabeculectomies, glaucoma drainage implants, and scleral buckles, which were previously excluded from the globe-preserving option., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin-angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)-associated conjunctival fibrosis., Methods: A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. Eyes were harvested at 4 and 8 weeks after the transplant for alpha-smooth muscle actin (α-SMA), angiotensinogen, and angiotensin-converting enzyme (ACE) immunostaining. Conjunctiva was harvested for gene expression quantification of α-SMA, angiotensinogen, and ACE., Results: More than 80% of the spleen cells in the recipient mice were chromosome Y positive, thus conforming successful engraftment. A significant decrease in tear secretion and a marked increase in corneal keratopathy score after allogeneic transplantation indicated the onset of ocular GVHD in these mice. A significant increase in α-SMA gene expression and the presence of a large number of α-SMA-positive cells was noted in the bulbar orbital conjunctiva of mice after allogeneic transplantation. Allogenic transplantation also caused a significant increase in the gene expression and protein expression of angiotensinogen and ACE in the subconjunctival eyelid area., Conclusions: Results of the present study demonstrate that GVHD-associated conjunctival fibrosis is accompanied by myofibroblast formation and activation of the local conjunctival RAS.

The rehabilitation of visual acuity with severe conjunctival fibrosis depends on ocular reconstruction with suitable conjunctival substitutes. In this study, we have developed poly(lactic acid) (PLA) electrospun nanofibrous membranes (EFMs) surface coated by cellulose nanofibrils (CNF) and/or silk peptide (SP). The CNF coating improved the hydrophilicity and the SP coating proliferated conjunctival epithelial cells (CjECs). To prevent post-operative infections, the composite scaffolds were loaded with levofloxacin (LF), constantly exerting efficient bactericidal effects. In in vivo evaluations, the PLA EFMs presented excellent therapeutic effects by promoting structural and functional restoration of conjunctiva after transplant. Even with reduced topical administration of antibiotics, the coloboma treated with LF loaded scaffolds presented no infections. It could be deduced that the potent bacterial inhibition feature could save troubles for patients by minimizing the application of antibiotics post-surgery. Hence, the developed PLA EFMs loaded with LF could be promising conjunctival substitutes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Purpose: In this study, we wanted to retrospectively evaluate the effect of the use of topical brimonidine on intraoperative bleeding and surgical hemostasis before strabismus surgery. Methods: Brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops were applied 6 and 3 min before surgery to 44 eyes of 22 patients in group 1 for vasoconstriction. Drops were not applied to 46 eyes of 23 patients in group 2. Preoperative and postoperative photographs and video images were taken. Black-and-white images were used to define the surface areas of the blood vessels. The surface area was calculated by counting the black pixels with ImageJ software. Results: In group 1, redness of eye was observed, on average, at preoperative 339.25 ± 11.52 pixels and intraoperative 247.93 ± 10.63 pixels ( P  < 0.001). But there was no change in group 2 (preoperative 338.87 ± 8.45 pixels to intraoperative 339.71 ± 9.52 pixels, P  > 0.05). The incidence of intraoperative bleeding evaluated by the number of eyes on which cautery was used shows that it was significantly less in group 1 than in group 2 ( P  < 0.001). Conclusions: The use of topical brimonidine before strabismus surgery facilitates clear monitoring of anatomical structures during surgery by effectively controlling hemorrhage. In the postoperative period, it significantly reduces subconjunctival hemorrhage.

Conjunctival orbital cysts are rare; they are typically either conjunctival dermoid or conjunctival epithelial cysts - congenital or acquired (inclusion). We describe the case of a 15-month-old girl presenting with strabismus and proptosis who had a retrobulbar intraconal cystic lesion displacing the optic nerve, with an adjacent middle cranial fossa anomaly. Aspiration of the orbital cyst tested positive for asialotransferrin, raising the suspicion of a direct communication with cerebrospinal fluid (CSF). Subsequent fine cut CT scanning disproved any connection with the intracranial space, and the cyst was excised complete and intact. Histopathology showed a conjunctival epithelial cyst. To our knowledge, this is the first case report in the literature of an asialotransferrin positive pediatric orbital conjunctival epithelial cyst. It is of clinical relevance as it explores the possibility of either a false positive asialotransferrin or potentially a prior developmental communication with the subarachnoid space. These two diagnostic possibilities are discussed.

To evaluate the ocular manifestation in patients hospitalized with coronavirus disease 2019 (COVID-19) and to search for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears. This study was conducted in 29 hospitalized patients who were admitted to the COVID center at the Policlinic Hospital of the University of Messina, Italy. All patients underwent an ophthalmologic assessment comprising a Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire, anterior segment, and the ocular surface examination of both eyes using a portable slit lamp. The Schirmer I test was performed, and the filter paper strip was used to search for the presence of SARS-CoV-2 on the ocular surface by real-time quantitative polymerase chain reaction (RT-qPCR). A total of 10 patients reported ocular symptoms; in particular, four reported eye burning, three reported foreign body sensation, and three reported tearing. Moreover, seven patients presented conjunctival hyperemia and/or chemosis, eleven patients presented blepharitis signs such as lid margin hyperemia and/or telangiectasia, crusted eyelashes, and meibomian orifices alterations. Tear analysis did not reveal the presence of SARS-CoV-2. Ocular symptoms are common in patients with COVID-19; although, tear analysis did not reveal the presence of SARS-CoV-2.

Purpose: In recent decades, the medical and surgical treatment of limbal stem cell deficiency (LSCD) has evolved significantly through the incorporation of innovative pharmacological strategies, surgical techniques, bioengineering, and cell therapy. With such a wide variety of options, there is a need to establish a global consensus on the preferred approaches for the medical and surgical treatment of LSCD., Methods: An international LSCD Working Group was established by the Cornea Society in 2012 and divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to reach agreement on a strategic plan and methods after a comprehensive literature search. A writing group drafted the current study., Results: A consensus in the medical and surgical management of LSCD was reached by the Working Group. Optimization of the ocular surface by eyelid and conjunctival reconstruction, antiinflammatory therapy, dry eye and meibomian gland dysfunction treatment, minimization of ocular surface toxicity from medications, topical medications that promote epithelialization, and use of a scleral lens is considered essential before surgical treatment of LSCD. Depending on the laterality, cause, and stage of LSCD, surgical strategies including conjunctival epitheliectomy, amniotic membrane transplantation, transplantation of limbal stem cells using different techniques and sources (allogeneic vs. autologous vs. ex vivo-cultivated), transplantation of oral mucosal epithelium, and keratoprosthesis can be performed as treatment. A stepwise flowchart for use in treatment decision-making was established., Conclusions: This global consensus provides an up-to-date and comprehensive framework for the management of LSCD.

Background: The coronavirus disease 2019 (COVID-19) has reportedly affected almost 23 million people, with more than 800 thousand deaths globally. There have been a few reports on the ocular manifestations of COVID-19 patients in China but no reports in Korea. The present study aimed to examine ocular manifestations of COVID-19 patients in Korea., Methods: COVID-19 patients admitted from March 2020 to April 2020 at Keimyung University Dongsan Hospital and Keimyung University Daegu Dongsan Hospital were reviewed retrospectively for ocular manifestations. During the period of hospitalization, ocular symptoms as well as blood test results were noted and analyzed. Patients were then divided into the first-episode and relapsed group and ocular symptoms were analyzed in the groups., Results: A total of 103 patients were included in this study. Among them, 71patients were in the first-episode group and 32 patients in the relapsed group. No significant differences were determined in terms of positivity of ocular symptoms between the first-episode group (12 patients, 16.9%) and the relapsed group (10 patients, 31.3%, P > 0.05). Symptoms of positive upper respiratory infection and lower creatine phosphokinase were determined to be related to positive ocular symptoms. Conjunctival congestion was noted in seven patients. In the subgroup analysis, the conjunctival congestion-positive patients exhibited higher positivity of upper respiratory infection symptoms (100%) as compared with those in the negative group (40%, P = 0.017)., Conclusion: Positive upper respiratory infection symptoms and lower creatine phosphokinase were determined to be related to ocular symptoms in COVID-19 patients. Among these patients, positive upper respiratory infection symptoms were associated with conjunctival congestion., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

BACKGROUND Eosinophilic angiocentric fibrosis (EAF) is an extremely rare disease with characteristic histopathological findings of fibrotic onion-skin appearance and eosinophils. The lesion primarily affects the nasal cavity, paranasal sinus, and orbit. Although there have been approximately 78 cases of EAF reported in the literature to date, no cases of EAF in the eyelid conjunctiva have ever been reported. CASE REPORT Herein, we describe the case of a 55-year-old Japanese woman with a history of eosinophilic sinusitis and EAF in bilateral upper eyelid conjunctivas who underwent surgical resection of the affected tissue. Histopathological examination revealed collagen bundles winding around the vessels in an onion-skin pattern, and the presence of eosinophils, lymphocytes, and plasma cells. CONCLUSIONS We describe the first reported case of EAF in bilateral upper eyelid conjunctivas. It can be successfully treated by surgical resection, and with no recurrence within 6 months postoperatively.

Purpose: Rho-associated kinase-inhibitor ripasudil 0.4% eye drops are reportedly effective for the reduction of intraocular pressure (IOP) in glaucoma patients. However, the previous studies investigated the efficacy of IOP reduction for only about 1 year. Here, we evaluated the safety and efficacy of long-term ripasudil instillation in Japanese open-angle glaucoma (OAG) patients. Methods: This study involved 312 eyes of 312 Japanese OAG patients newly initiated with ripasudil treatment at Kyoto Prefectural University of Medicine and Oike-Ikeda Eye Clinic, Kyoto, Japan. In all patients, adverse events leading to discontinuation of ripasudil treatment were investigated. Of the 312 patients, 129 patients able to continue ripasudil administration for over 12-months post-treatment initiation were enrolled to investigate the long-term efficacy. IOP data at 0-, 1-, 3-, 6-, 12-, 18-, and 24-months post initiation of continuous ripasudil use were obtained, and the IOP values at each time point were then compared. The first period (from 1-6 months) and second period (from 12-24 months) IOP data were also compared based on the mixed model. Results: IOP at each time-point post-treatment initiation was significantly reduced compared with that at pre initiation ( P  < 0.05). Differences in IOP between the first and second periods of the study were not statistically significant ( P  = 0.058). Adverse events leading to discontinuation of treatment included blepharitis (15.7%) and conjunctival hyperemia (9.0%). Conclusions: We found that in Japanese OAG patients, 24-month ripasudil eye drop instillation is both safe and effective for lowering IOP and that blepharitis is the primary adverse event for discontinuation of use.

Competing Interests: None

A 5-year-old otherwise healthy girl presented to the oculoplastic service with a painless superotemporal subconjunctival mass in the left eye. Visual acuity was within normal limits, and there was no evidence of proptosis or orbital enlargement. Excision was performed to remove the anterior portion of the mass for alleviation of symptoms. On histopathological analysis, the mass was comprised of fibroadipose tissue consistent with dermolipoma and contained a hard nodule found to be a calcified tooth. In the periocular region, odontogenic choristoma (tooth) is a rare lesion, and has been reported to occur within teratomas, dermoid cysts, and displaced oral embryonic epithelium. We describe an unusual case of a tooth occurring within a sporadic dermolipoma. The clinical presentation, examination, management, and histopathology are reviewed.

Purpose: Conjunctivochalasis (CCH) is a common ocular disease and has received extensive attention recently. However, its exact pathogenesis remains largely unknown. Owing to the high morbidity of CCH in older people, this study aimed to investigate whether cellular senescence contributes to CCH progression and the underlying mechanism., Methods: Loose conjunctival tissues from CCH patients (n = 13) and normal conjunctival tissues from age-matched persons (n = 12) were obtained and the fibroblasts were separately induced and obtained. Cellular senescence, and the expression of senescence-associated genes (p53 and p21) and p38 in CCH conjunctival tissues and normal controls, were determined by senescence-associated β-galactosidase (SA-β-Gal) staining and quantitative (q)RT-PCR, respectively. To explore the effects of p38 on cellular senescence in CCH fibroblasts, small interfering RNA (siRNA) targeting p38 (siP38) and p38-specific inhibitor SB203580 was performed in CCH fibroblasts. Then, cellular senescence, cell viability, reactive oxygen species (ROS) production, and gene expression were detected according to the corresponding methods., Results: CCH conjunctival tissues had significantly more senescent cells, evidenced by more SA-β-Gal-positive cells, and higher expression of senescence-associated genes (p53 and p21) and p38. CCH fibroblasts transfected with siP38 or treated with SB203580 had obviously reduced numbers of senescent cells, decreased ROS production, and increased cell viability, as well as reduced expression of senescence-associated genes. Meanwhile, blocking p38 signaling decreased the expression of p53 and p21., Conclusions: Therefore, these findings indicate that cellular senescence might be a causative factor for CCH. P38 signaling might play an important role in the progress of cellular senescence in CCH fibroblasts via manipulation of p53/p21 signaling.

An 18-month-old Arabian-English filly resident in southwest France was referred for evaluation of a conjunctival mass in the right eye (OD). A pink, solid, and mobile nodular formation, measuring approximately 1.2 × 0.8 cm was found under the superior nasal bulbar conjunctiva during an ophthalmic examination that was otherwise normal. The mass was surgically removed using a standing procedure. Cytological examination of fine-needle aspirates from the mass revealed a mixed eosinophilic-lymphocytic inflammation. Histological examination confirmed the dense and diffuse eosinophilic-lymphocytic infiltrate of the mass, and it revealed several cross sections of a parasitic nematode. The morphometric diagnosis identified an immature form of a filarial worm, and molecular analysis of the mitochondrial cytochrome c oxydase subunit 1 (cox1) and 12S rRNA gene sequences led to further identification of the specimen as Setaria equina. Microfilaremia was not observed on fresh blood smears. There have been no signs of local recurrence after 18 months, nor any evidence of intraocular involvement. To the authors' knowledge, this is the first documented case of subconjunctival setariasis due to S equina in a horse., (© 2019 American College of Veterinary Ophthalmologists.)

Purpose: To describe a case series of periocular lobular capillary hemangiomas in adults, outlining characteristic clinical and histopathological patterns., Materials and Methods: This was a retrospective case series of 16 patients with review of clinical and histopathological features., Results: Eleven male and five female patients were diagnosed with periocular lobular capillary hemangioma at a median age of 38 years (mean, 41 years; range, 21-71 years). The median tumor basal diameter was 6 mm (mean, 7 mm; range, 3-14 mm) and all were well circumscribed. They arose over the course of weeks to months and developed most commonly in the eyelid region ( n = 10), followed by the conjunctiva ( n = 6). Excisional biopsy of the lesion was done in all cases. On histopathology, the tumors were composed of repeating units of capillary-sized lobules lined by plump endothelial cells. Lesion recurrence was noted in one case., Conclusion: Lobular capillary hemangiomas are common benign vascular tumors of periocular region in adults. Clinicohistopathological features and clinical presentation of these lesions are distinctive. Excisional biopsy was curative with recurrence noted rarely., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Middle East African Journal of Ophthalmology.)

We describe the clinical, histopathologic, and immunohistochemical characteristics of episcleral/conjunctival pseudorheumatoid nodulosis, a new granulomatous entity that belongs among a group of related lesions. Specifically, pseudorheumatoid nodulosis should be differentiated from solitary rheumatoid nodules, rheumatoid nodulosis, accelerated rheumatoid nodules and nodulosis, and solitary pseudorheumatoid nodules. A 53-year-old man presented with bilateral painless, large, faintly yellow-gray, partially immobile, solid, circumscribed, and occasionally confluent episcleral nodules of several months' duration. He had never had clinical rheumatoid arthritis and was rheumatoid factor negative. Biopsy revealed multiple, merging episcleral/conjunctival, nonulcerated, palisading granulomas with variably sized central zones of necrobiosis of collagen. Abundant palisading CD68/163 + histiocytes admixed with fibroblasts surrounded the necrobiotic foci, which failed to stain with Alcian blue for mucopolysaccharides. No fibrinoid deposits were detected. Numerous CD3+ T lymphocytes, fewer CD 20 + B lymphocytes, and a smaller subpopulation of CD138 + plasma cells were present. Numerous CD1a + Langerhans cells were scattered among the palisading histiocytes and overlying epithelium. Immunohistochemical stains for immunoglobulins revealed concentrations of IgG, IgM, and IgA, but not IgE, in the necrobiotic zones. Special stains did not reveal evidence of infection nor did polarization microscopy display any foreign material. An extensive systemic and serologic workup was negative. We review simulating palisading or other nonrheumatic granulomas that should be distinguished from pseudorheumatoid nodules or nodulosis and explore therapeutic options., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate changes in conjunctival tissue of conjunctivochalasis (CCh) patients and to determine the relationship between pathological findings and localization of loose conjunctiva., Methods: Our study included nineteen eyes of 19 patients who were referred to Cukurova University Ophthalmology Department based on ocular surface symptoms and CCh detected in ocular examination. Amniotic membrane was applied after conjunctival excision as surgical treatment. The control group was formed with five eyes of five patients who are similar in terms of age and gender distribution with our study group. Tissue samples obtained from the study and control groups were investigated with light and electron microscopy., Results: Results of pathological examination of conjunctival tissues revealed increased inflammation in 13 patients (68%), lymphatic ectasia in 12 patients (63%), and loss of goblet cells in 17 patients (89%). Destruction of elastic fibers was detected in all cases by staining with elastic van Gieson. After semiquantitative assessment, varying degrees of light microscopic findings were noted considering the localization of CCh. No statistically significant relationship was observed between light microscopic findings and CCh location (p > 0.05 for all). Electron microscopic investigation revealed increase in intercellular spaces, increased cytoplasmic electron density, and the presence of slight vacuolization in cell cytoplasm, and heterochromatin clumping in nuclei of cells in conjunctival samples., Conclusions: Mechanical and inflammatory factors induce development of CCh, and signs associated with these factors can be detected with light and electron microscopy of conjunctival tissue. No relationship was observed between CCh localization and pathological changes in tissues examined in our study, and large-scale case series are required to evaluate the possible effect of CCh localization on pathological findings.

Purpose: Chemokines play a role in the progression and metastatic spread of both cutaneous and uveal melanomas. The aim of this study was to examine the prognostic value of expression of chemokine receptors CCR7, CXCR4, and CCR10 in conjunctival melanocytic lesions., Methods: In total, 44 conjunctival nevi, 21 cases of primary acquired melanosis (PAM) with atypia and 35 conjunctival melanomas, were included. After immunohistochemical staining for CCR7, CXCR4, and CCR10 the immunoreactive score (IRS) was determined. The findings were correlated for association with melanoma and development of metastasis. For mechanistic evaluation, we used a mouse melanoma metastasis model using two human conjunctival melanoma cell lines, CM2005.1 and CRMM1., Results: All tested chemokines showed a significantly higher expression in conjunctival melanoma than conjunctival nevi. There was a statistically significant difference between the IRS in nevi and PAM with atypia for nuclear IRS in CCR10 (P = 0.03) and both nuclear and cytoplasmic IRS in CXCR4 (P < 0.01 and P = 0.03, respectively); this was also true evaluating the groups PAM with atypia and melanoma all together (P < 0.01). Furthermore, a trend for lower IRS was seen in cases of melanoma without metastasis, with a suggestive pattern of a higher IRS in cases that did develop metastases, supported for CXCR4 using the mouse melanoma metastasis model., Conclusions: Expression of specific chemokines changes during the progression and metastatic spread of conjunctival melanocytic lesions. Differential chemokine profiles may hold prognostic value for patients with conjunctival melanomas and might be considered as a therapeutic target.

Objective: To evaluate tissue levels, safety, and efficacy of topical ophthalmic 0.5% and 1% pirfenidone in decreasing subconjunctival fibrosis., Animal Studied: Twelve normal beagle dogs PROCEDURES: A 5 × 1 mm diameter silicone disk was implanted subconjunctivally in one eye, and then dogs were treated with topical 0.5% pirfenidone (n = 9) in artificial tears or artificial tears alone (n = 3) for 28 days. To evaluate tissue drug levels, a single sample of tears, conjunctiva, and aqueous humor was collected 30 (n = 3), 90 (n = 3), and 180 min (n = 3) following administration of the last drop of pirfenidone, respectively. Fibrous capsule thickness and staining for Ki67 and fibroblast activation protein alpha (FAPα) were evaluated histologically. After a 2-week washout, the experiment was repeated in the opposite eye and using 1% pirfenidone., Results: Treatment with pirfenidone resulted in thinner fibrous capsules and decreased staining for FAPα with no adverse effects. The implant in one dog treated with pirfenidone extruded. There was no difference in tissue levels, capsular thickness, or staining for Ki67 or FAPα between dogs treated with 0.5% or 1% pirfenidone., Conclusions: Pirfenidone may decrease fibrosis following glaucoma shunt surgery and can potentially be used indefinitely due to minimal side effects., (© 2019 American College of Veterinary Ophthalmologists.)

Purpose: To investigate the roles and pathways of microRNAs 143 and 145 in transforming growth factor (TGF)-β1-induced human subconjunctival fibrosis., Methods: Human tenon's capsule fibroblasts (HTFs) were obtained from a healthy eye. After treating cultured HTFs with TGF-β1, the expression of microRNAs 143 and 145 was evaluated using polymerase chain reaction. To identify the pathways of TGF-β1-induced microRNA 143/145 expression, HTFs were treated with specific inhibitors of p38MAPK, PI3K/Akt, JNK, ERK, and with siRNAs for SMAD2 and SMAD4. Mutagenesis studies were performed to evaluate the role of the CArG box and SMAD-binding element (SBE). To investigate the role of microRNA 143/145 in TGF-β1-induced myofibroblast transdifferentiation, microRNA 143/145 mimics and microRNA 143/145 inhibitors were applied to the HTFs., Results: Array analysis revealed that TGF-β1 induced the expression of microRNA 143/145 in a dose- and time-dependent manner. When inhibitors and siRNAs for p38MAPK, PI3K/Akt, ERK, and JNK were applied, the TGF-β1-induced expression of microRNA 143/145 was inhibited; however, SMAD2 and SMAD4 inhibition did not affect the TGF-β1-induced expression of these microRNAs. In the mutagenesis studies, both the CArG box and SBE were associated with TGF-β1-induced expression of microRNA 143/145. Mimics of microRNA 143/145 induced increased myofibroblast formation, whereas their inhibitors had the opposite effect., Conclusions: TGF-β1-induced human subconjunctival fibrosis was mediated by the expression of microRNA 143/145, mainly via SMAD-independent pathways. Inhibition of TGF-β1-induced microRNA 143/145 expression in HTFs might represent a novel strategy to prevent subconjunctival fibrosis.

Competing Interests: Competing interests: None declared.

Background/aims: Limbal stem cell deficiency (LSCD) is characterised by a marked decrease in limbal stem cells. It is classified primarily using subjective slit-lamp observations. In vivo confocal microscopy (IVCM) can non-invasively provide objective information on the condition of the limbal niche, the corneal epithelial basal cell density and the corneal sub-basal nerve plexus density (SND). We here used IVCM to evaluate changes in SND to improve LSCD classification., Methods: We evaluated and classified 38 patients (76 eyes, 44 with LSC and 32 control eyes) using the Rama, López-García and Deng (clinical and confocal) classifications and evaluated the concordance of the confocal and clinical classifications. We constructed a logistic regression model using multivariate analysis to correlate different degrees of conjunctivalisation with IVCM parameters and used receiver operating characteristic (ROC) curve analysis to establish the SND cut-off value with maximum diagnostic sensitivity and specificity., Results: The classification systems correlated moderately at best (kappa, 0.449). The corneal SND of cases (6469±6295 µm/mm 2 ) was less (p<0.001) than in controls (20911±4142 µm/mm 2 ). The SND, but not basal cell density, played a protective role against conjunctivalisation (OR, 0.069; 95% CI 0.008-0.619; p=0.01). An SND cut-off value of 17 215 µm/mm 2 yielded a sensitivity and specificity of 95.5% and 90.6%, respectively, for LSCD diagnosis., Conclusion: The density of the corneal sub-basal nerve plexus was inversely related to conjunctivalisation in LSCD. Further studies are needed to verify this and to elucidate the directionality between these factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the in vitro effects of 1-mM rebamipide ophthalmic solution on the expression of inflammatory cytokines and MUC5AC in Cu, Zn-superoxide dismutase-1 (SOD-1) knock-down conjunctival epithelium., Methods: Conjunctival epithelium from C57BL/6 wild-type mice was cultured and treated with rebamipide ophthalmic solution. Using cytometric bead array, we examined the levels of interleukin-(IL)-6, IL-10, IL-17, monocyte chemoattractant protein-1, interferon-γ (INF-γ), tumor necrosis factor, and IL-12p70 in the culture supernatants. The culture supernatants were obtained from the culture medium of nontreated or SOD-1 knock-down conjunctival epithelium using small interfering RNA (siRNA). In addition, ELISA was performed to ascertain the MUC5AC concentration in the culture medium., Results: After rebamipide ophthalmic solution was applied, IL-6 concentration in the supernatants of conjunctival epithelial cells treated with and without siRNA showed a significant timewise decrease from 0 to 24 hr (963±42 to 0.07±0.05 pg/mL and 932±168 to 2.2±0.05 pg/mL, respectively) (P<0.001). Compared with baseline values, MUC5AC concentrations significantly increased 24 hr after rebamipide application to the conjunctival cultures-both with and without SOD-1 siRNA treatment (P<0.05 in both cases)., Conclusions: Rebamipide seems to increase MUC5AC levels and suppress inflammation by decreasing IL-6 levels in mouse conjunctival epithelial cell cultures. SOD-1 siRNA-treated mouse conjunctival epithelial cell culture is a practical method for investigating changes in mucosa-associated mucins and proinflammatory cytokines in response to therapeutic interventions.

Purpose: To describe a rare case of conjunctival colloid milium., Methods: Case report., Results: We report a 45-year-old woman with a history of a slow-growing, painless mass extending from the medial canthal region to the inferior fornix and the inferior bulbar conjunctiva associated with redness. The patient underwent excisional biopsy of the lesion with amniotic membrane transplantation for the resulting conjunctival defect. Biopsy showed homogenous amorphous eosinophilic material with gaps. The stroma did not show any evidence of solar damage, and no refractive material was seen under the polarizer. Congo red stain for amyloid was negative. Based on histopathological findings, a diagnosis of nodular colloid milium was made., Conclusions: Adult periocular colloid milium is an unusual presentation of a rare cutaneous deposition disease. The occurrence of conjunctival colloid milium is rare, and we report this case to increase knowledge and management regarding this rare disease and to differentiate it from other diseases such as amyloidosis, lipoid proteinosis, plasmacytoma, and conjunctival lymphoma, which carry a graver prognosis, and have a similar clinical appearance and can be distinguished only on the basis of histopathological characteristics.

Objective: To compare the conjunctival morphological changes in patients with Hashimoto’s thyroiditis (HT) without thyroid-associated ophthalmopathy (TAO) and controls using impression cytology technique., Material and Method: We included 25 HT patients and 33 healthy controls who did not have TAO findings or dry eye. For both groups, thyroid stimulating hormone (TSH), free T4(FT4), and anti-thyroid peroxidase (anti-TPO) were measured. Thyroid ultrasonography was performed, together with all routine eye check-ups and the Schirmer’s test. Also, conjunctival impression cytology (CIC) test was performed to analyze the conjunctival morphology., Results: When the CIC of HT patients was observed; 12% had grade 0, 40% had grade 1, 28% had grade 2 and 20% had grade 3. While patients with squamous metaplasia made up 48% of the HT group, this was observed at 6.1% in the control group (p < 0,001). In the regression model formulated, it was observed that obesity (OR=7.500; p=0.017) and anti TPO levels (OR=1.370, p=0,007) were independent stipulations for the squamous metaplasia., Conclusion: Conjunctival squamous metaplasia was more frequently seen in HT than controls and serum Anti-TPO level and obesity were detected as independent predictors of the worsening at the conjunctival impression cytology.

We report the first case of invasive ophthalmologic infection by Acrophialophora sp. that was successfully treated using voriconazole (VRCZ). Acrophialophora spp., which has been reported to be an opportunistic pathogen, is a rare thermotolerant soil fungus, but its pathogenicity remains unclear. A 77-year-old man had neutropenia and prostate carcinoma and was receiving hemodialysis. His right eye had been infected for 2 days. His conjunctiva was congested, and it partially formed an abscess. Liposomal amphotericin B (L-AMB) was administered following systemic itraconazole. However, the treatment was changed from L-AMB to systemic VRCZ and VRCZ eye drops because his eye symptoms worsened. Subsequently, his symptoms stabilized and his vision was maintained. Acrophialophora sp. was identified by analyzing regions of internal transcribed spacer and domain 1 and 2 of the ribosomal RNA gene. He completed the 7-week systemic VRCZ course. The mean minimum inhibitory concentration of VRCZ for Acrophialophora spp. has been reported to be the lowest among various antifungal agents, and our results indicated the efficacy of VRCZ treatment for Acrophialophora sp. infection. Our results suggest that invasive Acrophialophora sp. infection may require long-term therapy. Further analysis of the clinical spectrum of Acrophialophora spp. infection and adequate treatment methods are required in the future.

Objectives: This study aimed to analyze the influencing factors of meibomian gland loss in patients with ocular chronic graft-versus-host disease (GVHD) and its correlation with other clinical ocular surface assessment indexes., Methods: The clinical data of patients with ocular chronic GVHD from the ocular surface and corneal outpatient clinic of the First Affiliated Hospital of Soochow University were reviewed from June 2012 to June 2016. The relationship between the percentage of meibomian gland acinar area and the influencing factors, such as patient's sex, age, transplantation method, human leukocyte antigen (HLA) matching, the time when eye discomfort appeared after transplantation (month), and the severity of ocular chronic GVHD, was investigated. Moreover, the correlation between the percentage of meibomian gland acinar area and other ocular surface assessment indexes, such as subjective ocular symptom score, eyelid margin score, tear film break-up time, corneal and conjunctival staining score, and the Schirmer test, was analyzed., Results: A linear relationship was found between the percentage of meibomian gland acinar area and the severity of ocular chronic GVHD, but no linear relationship existed between the percentage of meibomian gland acinar area and the factors such as sex, age, transplantation method, HLA matching, and the time when eye discomfort appeared after transplantation. A negative correlation was observed between the percentage of meibomian gland acinar area and eyelid margin score., Conclusions: The percentage of meibomian gland acinar area can reflect the severity of ocular chronic GVHD. The clinical significance of the percentage of meibomian gland acinar area needs further investigation.