Atypical presentation of a lymphangioma as a conjunctival horn.

Conjunctival lymphangiomas are rare hamartomas of lymphatic origin that are usually located in the bulbar conjunctiva. They commonly present either as focal or diffuse bulbar chemosis or as dilatation of lymphatic vessels that resembles an isolated cyst or a group of cysts. There can be bleeding inside the lymphangioma resulting in "chocolate cysts".1 We report the unusual case of a conjunctival lymphangioma on a 36 year-old male that presented as a large horn-like protruding structure. The lesion was surgically removed with simple excision associated with cryotherapy to the lesion's borders, as malignancy could not be ruled out preoperatively. Histopathological examination revealed a lymphangioma composed of an ill-defined proliferation of dilated lymphatic channels in the lamina propria, underlying conjunctival epithelium with squamous metaplasia, acanthosis and hyperkeratosis. One year postoperatively, the patient remains asymptomatic and without recurrence of the lesion.

A detailed survey of the murine limbus, its stem cell distribution, and its boundaries with the cornea and conjunctiva.

The narrow intersection between the cornea and conjunctiva, otherwise known as the limbus, is purported to harbor stem cells (SCs) that replenish the ocular surface epithelium throughout life. Damage to this site or depletion of its SCs can have dire consequences for eye health and vision. To date, various SC and keratin proteins have been used to identify the limbus, however, none could definitively mark its boundaries. Herein, we use the mouse as a model system to investigate whether structural and phenotypic features can be used to define the limbus and its boundaries with adjacent tissues. We demonstrate that differentially aligned blood and lymphatic vessels, intraepithelial nerves, and basal epithelial cellular and nuclei dimensions can be used as structural landmarks of the limbus. Identification of these features enabled approximation of the limbal expanse, which varied across distinct ocular surface quadrants, with the superior nasal and inferior temporal limbus being the widest and narrowest, respectively. Moreover, label-retaining SCs were unevenly distributed across the ocular circumference, with increased numbers in the superior temporal and inferior temporal moieties. These findings will heighten our current understanding of the SC niche, be beneficial for accurately predicting SC distribution to improve their isolation and devising efficacious cell therapies, and importantly, aid the ongoing search for novel SC markers.

Clinical applications of in vivo confocal microscopy enhance the detection and management of ocular surface disease in dogs and cats.

In vivo confocal microscopy (IVCM) is a unique imaging technique that permits noninvasive evaluation of the ocular surface on the cellular level. High-resolution images of all layers of the cornea are obtained in real-time with IVCM, and the acquired images are often comparable to ex vivo histochemical analysis of corneal biopsy specimens. The basic morphological features of the healthy living cornea as viewed by IVCM are reported in many domestic animal species, and the number of published descriptions of ocular surface pathologies in companion animals is progressively expanding. There is great potential for IVCM to improve the detection, characterization, and management of diverse ocular surface diseases in companion animals. This review summarizes several established and emerging clinical applications of IVCM in companion animal ocular surface disease, including infectious keratitis, corneal foreign bodies, corneal dystrophies and degenerations, ocular surface masses, corneal endotheliitis, pigmentary keratitis, and evaluation of corneal nerves.

Congenital eyelid imbrication syndrome: A rare occurrence in Pakistan.

Congenital eyelid imbrication syndrome (CEIS) is a rare condition presenting at birth and is characterised by overriding of the upper lid on the lower lid. It is due to longer upper lid, than the lower lid. Overriding leads to spontaneous eversion of the upper lids. In our patient, examination revealed canthal tendon laxity and hyperaemia of the tarsal conjunctiva. All the rest of the structures in the eyeball and adnexa were normal. Spontaneous eversion occurred in two weeks as the upper lid grew with time. No treatment was required.

Discriminative performance of ocular surface staining and lid wiper epitheliopathy in dry eye disease: An investigator-masked, prospective registry-based, diagnostic accuracy study.

PURPOSE: To evaluate the diagnostic performance of corneal and conjunctival staining, and lid wiper epitheliopathy (LWE) in detecting dry eye disease, as defined by the global consensus Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) criteria. METHODS: A total of 2066 community residents (1285 females; mean ± SD age, 40 ± 19 years) were recruited in an investigator-masked, prospective registry-based, diagnostic accuracy study. Dry eye symptomology and ocular surface parameters were assessed in a single clinical session. The Sjögren's International Collaborative Clinical Alliance (SICCA) corneal and conjunctival staining scoring and Korb lid wiper epitheliopathy (LWE) grading were evaluated by an independent masked assessor. RESULTS: Overall, 807 (39 %) participants fulfilled the TFOS DEWS II criteria for dry eye disease, of which 178 (9 %) participants were classified as moderate-to-severe disease. The discriminative abilities of superior and inferior LWE (C-statistics, 0.724 and 0.712, respectively) were greater than corneal and conjunctival staining (C-statistics, 0.573 and 0.627, respectively). The Youden-optimal diagnostic cut-offs for the SICCA corneal and conjunctival staining scores were both ≥1, and the optimal thresholds for the Korb superior and inferior LWE grades were both ≥1. LWE was more commonly detected in both mild-to-moderate and moderate-to-severe dry eye disease, and demonstrated more consistent correlation with other ocular surface parameters across a broader range of disease severity. CONCLUSIONS: LWE demonstrates superior diagnostic performance relative to corneal and conjunctival staining. These findings would support the routine incorporation of LWE evaluation as part of the diagnostic workup of dry eye disease.

Ocular Surface Fluid: More than a Matrix.

Although the eye can be subjected to therapeutic manipulation, some of its structures are highly inaccessible. Thus, conventional therapeutic administration pathways, such as topical or systemic routes, usually show significant limitations in the form of low ocular penetration or the appearance of side effects linked to physiology, among others. The critical feature of many xenobiotics is the drug gradient from the concentrated tear reservoir to the relatively barren corneal and conjunctival epithelia, which forces a passive route of absorption. The same is true in the opposite direction, towards the ocular surface (OS). With the premise that tears can be regarded as equivalent to or a substitute for plasma, researchers may determine drug concentrations in the OS fluid. Within this framework, a survey of scholarly sources on the topic was conducted. It provided an overview of current knowledge, allowing the identification of relevant theories, methods, and gaps in the existing research that can be employed in subsequent research. OS fluid (tears particularly) has enormous potential as a source of biological material for external drug screening and as a biomarker of various systemic diseases. Given the numerous alternate matrices, knowledge of their properties is very important in selecting the most appropriate specimens in toxicological analyses.

Clinical analysis of 37 Chinese patients with ocular amyloidosis: a single center study.

OBJECTIVE: To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population. METHODS: A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed. RESULTS: The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up. CONCLUSION: Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary.

Tuck-in tenon patch graft for giant full-thickness macular holes.

PURPOSE: To report the results of using autologous Tenon patch grafts for managing giant full-thickness macular holes (FTMHs) when other alternatives are not applicable. METHODS: The same surgical technique was performed in all three cases. Briefly, a small fragment of Tenon's tissue was collected. The graft was introduced through a 23G trocar and released over the macular hole under a bubble of PFCL. The patch is delicately pushed towards the edges of the hole to slide underneath. The PFCL bubble is then actively aspirated next to the optic disc. Tamponade with gas or silicone oil is subsequently injected, with care taken to minimize fluid turbulence during the procedure. RESULTS: The outcomes of autologous Tenon patch grafts in three giant FTMHs are reported. In the first case, silicone oil tamponade was injected, in the second, C2F6 gas was injected. And in the third case, that of a woman with advanced glaucoma, no tamponade was left in the eye. No adverse effects were observed during or after the procedures. Closure of the macular hole and functional improvement were documented during the follow-up period in all three cases. CONCLUSION: With a follow-up of up to 6 months, the Tenon patch graft appeared to be a promising technique for managing complex cases of FTMH. Additional studies to investigate long-term outcomes and determine the most appropriate indications are warranted.

Upper Eyelid Contour Changes After Müller's Muscle Conjunctiva Resection.

PURPOSE: To analyze the upper eyelid contour after Müller's muscle conjunctiva resection (MMCR) performed by four different surgeons. METHODS: Comparative cross-sectional analysis of the pre- and postoperative contours of a control group and four groups of upper lids (n = 88) of 65 patients who underwent MMCR at four international centers. The procedure employed was essentially the same as described by Putterman but performed with different instruments to entrap the posterior lamella. Multiple medial and lateral margin lid distances were measured on Bézier lines expressing the pre- and postoperative lid contours. RESULTS: Preoperatively, two groups had significant lateral and medial ptosis. After MMCR, the lateral segment of the lid's contour was corrected in all groups. In the two groups with more pronounced ptosis, the nasal lid contour was undercorrected. CONCLUSIONS: In MMCR, regardless of the instrument used to entrap the posterior lamella, the amount of medial tissue resection is essential to avoid postoperative nasal undercorrection. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The lateral fornix orbitotomy: a novel surgical corridor to lacrimal gland lesions.

PURPOSE: Current practice for diagnostic biopsy of lacrimal gland lesions entails an orbitotomy procedure via an upper eyelid crease or lateral canthotomy skin incision. We describe a novel surgical technique to address these lesions via the lateral conjunctival fornix. METHODS: Retrospective case series of all patients who underwent a lateral fornix orbitotomy procedure for incisional or excisional diagnostic biopsy of lacrimal gland lesions. The procedure involves a conjunctival incision in the lateral fornix remote from the openings of the lacrimal ductules, and an intraperiosteal surgical corridor to access the lacrimal gland. RESULTS: The study cohort included 16 patients (3 male, 13 female) with a mean age of 48.3 years (range, 24.0-78,9 years). The sampled lesions involved the orbital lobe in 14 patients, the palpebral lobe in 1 patient, and the entire gland in 1 patient. A histopathological diagnosis was obtained in all cases. Postoperatively, new moderate adduction deficit developed in one patient (6.3%) that recovered after adhesiolysis of the conjunctival scar. 3 patients (18.8%) experienced transient mild limitation of adduction or abduction. There was no new or worse ptosis or dry eye disease related to the surgery. The mean length of postoperative follow-up was 1.3 years (median 1.0 years, range, 0.6-4.7 years). CONCLUSION: The lateral fornix orbitotomy approach was successful in obtaining biopsy specimens of histopathological diagnostic value. It provides transconjunctival access to the lacrimal gland without damage to the excretory lacrimal ductules or displacement of the eyelid support system.

Ocular inflammation in tsutsugamushi disease - a case report.

A 64-year-old male, working at a mountain site in Taitung County, suffered from primary open angle glaucoma (POAG) post trabeculectomy with well-controlled intraocular pressure (IOP) in both eyes (OU). He presented with headache accompanied by red eyes (OU) for 10 days. Physical examination revealed fever up to 38.2°C, neck stiffness, one eschar at the left forearm and another at the left ankle. Abnormal laboratory data indicated bacterial infection with central nervous system involvement. Ophthalmic examination showed elevated IOP, moderate conjunctival congestion, subconjunctival hemorrhage, anterior uveitis, cotton-wool spots on the retina and multiple white dots on the temporal retina (OU). Under the impression of uveitis in tsutsugamushi disease with atypical meningitis, oral doxycycline, anti-glaucoma and anti-inflammation eye drugs were prescribed. IOP returned to 12 mmHg and anterior uveitis subsided. The lesions of cotton-wool spots on the retina disappeared within 2 weeks, but multiple white dots remained persistently on the temporal retina.

Primary ocular adnexal mantle cell lymphoma with distant spread and involvement of the contralateral eye one year later; a case report and literature review.

We herein report a middle-aged gentleman who initially presented with ocular adnexal mantle cell lymphoma (MCL) on the right eyelid. The lesion was excised and the patient was treated with radiation therapy. During the initial presentation, a PET CT was performed and did not reveal disease involvement beyond the eyelid. The patient presented 3 months later with ocular adnexal MCL of the contralateral eye. Re-evaluation using PET CT revealed a slight increase in the uptake in several lymph nodes and the spleen, which, after biopsy, confirmed systemic MCL. The patient was started on six cycles of chemotherapy. The patient also underwent autologous hematopoietic stem cell transplant. Approximately 80% of primary ocular adnexal lymphomas are B-cell in origin, with MCL being the rarest subtype constituting only 5% of B-cell ocular adnexal lymphomas. Despite its rarity, it is crucial for clinicians to detect the entity early and ensure rapid initiation of appropriate therapy.

Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

OBJECTIVE: To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3 weeks off regimen. RESULTS: Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52 years; range, 11-87 years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6 months (median, 5 months; range, 1-36 months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). CONCLUSION: Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Primary Leiomyosarcoma of the Orbit and Conjunctiva: A Report of Four Cases With a Review of the Literature.

Leiomyosarcomas (LMS) are common soft tissue tumors in the body. Primary orbital and conjunctival LMS are, however, rare. Herein, we describe the diverse clinical presentations, histopathological features, and management outcomes of three cases of primary LMS of the conjunctiva and one case of primary orbital LMS. The first patient was a 40-year-old female with primary orbital LMS who developed recurrence following wide local excision. The remaining three cases were primary conjunctival LMS. All four patients underwent orbital exenteration and were disease-free at a mean follow-up period of 18.64 months. LMS is known for local recurrences and metastasis. Complete surgical excision and prompt adjuvant radiotherapy can improve the prognosis.

Localized conjunctival amyloidosis clinically presenting as pyogenic granuloma.

Primary amyloidosis of the conjunctiva and eyelid is a rare and often misdiagnosed condition. It is characterized by the deposition of insoluble amyloid fibrils, which are misfolded proteins, in the body. Amyloidosis can be systemic or localized with different types of amyloid fibril proteins identified using mass spectrometry. Ocular involvement in amyloidosis can lead to corneal dystrophies, glaucoma, vitreous opacities, and other symptoms. Diagnosis involves clinical examination and histopathological assessment. Treatment options depend on the extent of involvement and may include surgical excision, glaucoma management, vitrectomy, or liver transplantation in rare cases. We present a rare case of localized conjunctival amyloidosis initially misdiagnosed as pyogenic granuloma, with clinical symptoms of ptosis, periorbital swelling, and conjunctival lesions. The patient underwent excision of the lesions, and subsequent evaluation did not reveal systemic amyloidosis. Ocular amyloidosis requires careful diagnosis and consideration of systemic involvement for appropriate management.

Incidence and Mitigation of Corneal Pseudomicrocysts Induced by Antibody-Drug Conjugates (ADCs).

Purpose of Review: This study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs). Recent Findings: ADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity. Summary: Three of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.

Intraocular Invasion by Conjunctival Squamous Cell Carcinoma: Clinical Presentation, Histopathological Findings, and Outcome.

Introduction: Intraocular localization of conjunctival squamous cell carcinoma (SCC) is due to scleral or corneal invasion. Herein, we describe the clinical and histopathological findings in four cases of SCC complicated by intraocular invasion, and we review cases reported in the literature and their management. We retrospectively collected and analyzed clinical characteristics, histopathology, management, and follow-up data from 4 patients with conjunctival SCC complicated by intraocular invasion. We reviewed the literature and summarized cases of intraocular invasion by conjunctival SCC reported over the last 30 years. Case Presentations: Two patients presented with intraocular invasion by conjunctival SCC at diagnosis. The two others developed intraocular invasion as recurrence of conjunctival SCC, previously treated with excisional biopsy and adjuvant radiotherapy. All 4 cases had a previous history of conjunctival surgery, but no history of intraocular surgery. Three patients were managed with modified enucleation, including one that required adjuvant orbital radiotherapy. One patient required orbital exenteration. Histopathology analysis showed a well-differentiated conjunctival SCC in all cases. None developed distant localization after at least 2.5-year follow-up. Discussion/Conclusion: Intraocular invasion is a rare complication of conjunctival SCC. Appropriate treatment in a tertiary center and long-term follow-up are highly recommended.

Ocular surface immune transcriptome and tear cytokines in corneal infection patients.

Background: Microbial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions' pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears. Methods: Corneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1ß, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay. Results: A total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) <-2 or > 2 and adjusted p <0.01). For the conjunctiva, 477 were upregulated, and 3 were downregulated (FC <-3 or ≥ 3 and adjusted p <0.01). There was a significant overlap in cornea and conjunctiva gene expression in patients with corneal infections. The genes were predominantly associated with immune response, regulation of angiogenesis, and apoptotic signaling pathways. The most highly upregulated gene was CXCL8 (which codes for IL-8 protein). In patients with corneal infections, the concentration of IL-8 protein in tears was relatively higher in patients compared to healthy controls but did not show statistical significance. Conclusions: During corneal infection, many genes were upregulated, with most of them being associated with immune response, regulation of angiogenesis, and apoptotic signaling. The findings may facilitate the development of treatments for corneal infections that can dampen specific aspects of the immune response to reduce scarring and preserve sight.

Diagnostic Accuracy of Conjunctival Rt-Pcr in Sars-Cov-2: A Systematic Review and Diagnostic Accuracy Meta-Analysis.

PURPOSE: To study the positivity rate of conjunctival realtime polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN: Systematic review and diagnostic accuracy meta-analysis. METHODS: MEDLINE and EMBASE were queried using medical subject headings terms. Diagnostic accuracy meta-analyses and forest plots were obtained using the RevMan software. RESULTS: After deduplication, appraisal of abstract titles and full-text analysis of 1441 articles, 42 articles with 3351 COVID-19 patients were included in this review. Of these, 412 conjunctival swabs/Schirmer paper strips tested positive for SARS-CoV-2 by RT-PCR. The pooled sensitivity of the RT-PCR tests across the 24 studies with laboratory-confirmed COVID-19 patients was 10.3%. CONCLUSIONS: Only 1 in 10 RT-PCR tests performed on conjunctival swabs were positive for SARS-CoV-2. Although this suggests that SARS-CoV-2 is likely present and detectable in the conjunctiva, this detection method has low diagnostic potential.

Blue light induced ferroptosis via STAT3/GPX4/SLC7A11/FTH1 in conjunctiva epithelium in vivo and in vitro.

The prevalence of Light-emitting diodes (LEDs) has exposed us to an excessive amount of blue light (BL) which causes various ophthalmic diseases. Previous studies have shown that conjunctiva is vulnerable to BL. In this study, we aimed to investigate the underlying mechanism of BL-induced injury in conjunctiva. We placed C57BL/6 mice and human conjunctival epithelial cell lines (HCECs) under BL (440 nm ± 15 nm, 0.2 mW/cm2) to establish a BL injury model in vivo and in vitro. Immunohistochemistry and MDA assay were used to identify lipid peroxidation (LPO) in vivo. HE staining was applied to detect morphological damage of conjunctival epithelium. DCFH-DA, C11-BODIPY 581/591, Calcein-AM, and FeRhoNox™-1 probes were performed to identify ferroptosis levels in vitro. Real-time qPCR and Western blotting techniques were employed to uncover signaling pathways of blue light-induced ferroptosis. Our findings demonstrated that BL affected tear film instability and induced conjunctival epithelium injury in vivo. Ferrostatin-1 significantly alleviated blue light-induced ferroptosis in vivo and in vitro. BL downregulates the levels of solute carrier family 7 member 11 (SLC7A11), Ferritin heavy chain (FTH1), and glutathione peroxidase (GPX4) by inhibiting the activation and translocation of the Signal transducer and activator of transcription 3 (STAT3) from inducing Fe2+ burst, ROS and LPO accumulation, ultimately resulting in ferroptosis. This study will offer new insight into BL-induced conjunctival injury and LED-induced dry eye.