Ocular tuberculosis presenting with a conjunctival granuloma.

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.

Congenital Conjunctival Cysts of the Orbit.

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.

Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease-Associated Conjunctival Fibrosis.

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.

Insight into levofloxacin loaded biocompatible electrospun scaffolds for their potential as conjunctival substitutes.

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.

The Results of Preoperative Use of Topical Brimonidine in Strabismus Surgery.

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.

Characteristics of Ocular Manifestations of Patients with Coronavirus Disease 2019 in Daegu Province, Korea.

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.

Global Consensus on the Management of Limbal Stem Cell Deficiency.

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.

Paediatric orbital conjunctival epithelial cyst with positive asialotransferrin.

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.

Periocular Lobular Capillary Hemangioma in Adults: A Clinicopathological Study.

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.

Changes in Conjunctiva Morphology Using Impression Cytology in Patients with Hashimoto's Thyroiditis without Thyroid-Associated Ophthalmopathy

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.

Chemokine Receptor Expression Pattern Correlates to Progression of Conjunctival Melanocytic Lesions.

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.

Brimonidine-induced unilateral ocular lichen planus: a case report / Líquen plano ocular unilateral induzido por brimonidina: relato de caso

ABSTRACT This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

RESUMO Este relato é para descrever um caso de líquen plano conjuntival unilateral induzido por brimonidina. Como o exame oftalmológico indicava conjuntivite crônica ou pseudopenfigóide induzido por medicamento, o paciente foi submetido a exames oftalmológicos e sistémicos completos, além de biópsia conjuntival e estudos de imunofluorescência direta. Uma mulher de 71 anos de idade com achados unilaterais do olho esquerdo de conjuntivite crônica foi encaminhada ao nosso departamento de Oftalmologia. A paciente relatou que a conjuntivite crônica começou logo após o início do uso da brimonidina tópica. O exame oftalmológico revelou encurtamento do fórnice inferior e do symblepharon. A biópsia conjuntival revelou linfócitos submucosos e distribuição felpuda de fibrinogênio na imunofluorescência direta; isso era sugestivo de líquen plano ocular. Não foram encontradas outras lesões sistêmicas compatíveis com a apresentação do líquen plano. Uma boa resposta foi observada no tratamento tópico com ciclosporina. Pelo nosso conhecimento, este pode ser o primeiro relato de líquen plano ocular unilateral sem achados sistêmicos. A correlação com o início da brimonidina tópica sugere que este pode ser o primeiro caso de líquen plano ocular induzido por brimonidina confirmado por biópsia.

Brimonidine-induced unilateral ocular lichen planus: a case report.

This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

Safety and efficacy of topically applied 0.5% and 1% pirfenidone in a canine model of subconjunctival fibrosis.

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.

Bilateral epibulbar pseudorheumatoid nodulosis with a review of ocular adnexal palisading granulomas.

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.