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To assess the efficacy of topical interferon α-2β(IFN) eye drops as a primary treatment for ocular surface squamous neoplasia(OSSN) and evaluate factors that impact response to treatment and recurrence of OSSN.A retrospective study of 143 OSSN patients treated with topical IFN(1MIU/ml) from January 1998 to June 2021. The diagnosis was based on clinical examination and anterior segment optical coherence tomography, with histologic confirmation was present in 46.2% of patients. Data on demographic, tumor characteristics, treatment outcome, and side effects were collected. The primary outcomes were tumor resolution frequency and recurrence rate. Secondary outcomes were predictive factors for resolution and recurrence and side effects of treatment.Participants were mostly older (mean age, 69 years, SD 12.9, range 29-97), white(89%) males (74%). Complete tumor resolution was achieved in 80.4% of individuals with a mean time to resolution of 4.2 months (SD 2, range 0.5-12.3 months). On multivariable analysis, history of skin cancer (HR: 0.66, p = 0.05, 95%CI: 0.44-0.99) and immune system abnormalities (HR: 0.37, p = 0.009, 95%CI: 0.18-0.79) reduced the risk of tumor resolution, while a prior history of OSSN (HR: 3.49, p 0.001, 95%CI: 1.76-6.93) increased the risk of resolution. With a mean follow-up time of 44.3 months (SD 50.9, 0-290 months), the recurrence rate was 0%, 2.3% and 3.1% at 1, 2, and 5 years respectively. Mild hyperemia(18.9%) and pain(10.6%) were the two most common side effects.Topical IFN eye drops are a safe and effective primary treatment modality for OSSN with a reasonable side effect profile.

To determine the efficacy and safety of topical 1% 5-fluorouracil (5FU) eye drops as primary treatment of ocular surface squamous neoplasia (OSSN).Patients were diagnosed with OSSN based on slit-lamp examination and anterior segment optical coherence tomography (AS-OCT). In ambiguous cases an incisional biopsy was performed. All were treated with 5FU eye drops as primary therapy and retrospectively reviewed. Data on demographics, tumor characteristics, treatment outcome, and side effects were collected. The primary outcome measures were resolution frequency and recurrence rate of OSSN. Secondary outcomes were risk factors for resolution and recurrence, and side effects of treatment.The mean age of 251 subjects (258 eyes) was 67.5 ± 11.7 years, 182 were male. Patients were followed up on average for 752 ± 580 days. Overall, 87% of patients experienced complete tumor resolution. Multivariable analysis revealed that superior tumor location (HR: 0.62, 95% CI: 0.41-0.93, p = 0.02) and leukoplakia (HR: 0.65, 95% CI: 0.41-0.93, p = 0.02), decreased the likelihood of tumor resolution. The recurrence rate was 4% at six months, 8% at one year, and 19% at two years. Larger tumor area increased chances of tumor recurrence (HR: 1.01, 95% CI: 1.00-1.02 p = 0.03). The most common side effects of 5-FU were mild hyperemia and pain, which occurred in 26% and 23% of patients, respectively. Among the sight-threatening side effects, limbal stem cell deficiency occurred in only 3% of patients.Topical 1% 5FU eye drops are a safe and effective medication for OSSN. Superior tumor location and leukoplakia decreased the chance of tumor resolution.

Conjunctival papilloma is often resistant to treatment. Various therapies have been reported with no gold standard. The purpose of this study was to compare treatment outcomes after various therapies.A retrospective chart review of 30 conjunctival papilloma patients from 2009-2020. Data on demographics, tumour characteristics, primary treatment and outcomes were collected. The primary outcome was the frequency of complete tumour resolution and recurrence rate of each primary therapy. The secondary outcome was treatment related side effects.The mean age was 57.5 years (3-93 years) with male predominance (n = 22, 73.3%). Eleven eyes were treated with interferon α-2b (IFN), seven with 5-fluorouracil (5FU), and 10 with excision biopsy and cryotherapy (6 with adjuvant therapy with IFN). The frequency of tumour resolution was 36.4% (4/11), 28.5% (2/7), and 100% (10/10) in each group, respectively. The mean time to resolution was faster in the surgical group compared to the medical group (1 day vs 159 days, p 0.001). There was higher tumour recurrence with 11% in the surgical vs 0% in the medical group at 6 months and at 12 months, 22% recurrence in the surgical and 0% in the medical group (p = 0.52). However, the differences were not statistically significant.Papilloma resolution is faster with surgical excision as compared to medical therapy. However, recurrences are more frequent after surgical versus medical treatment.

To describe the anterior segment optical coherence tomography (AS-OCT) appearance of conjunctival papilloma and identify differentiating features from papilliform ocular surface squamous neoplasia (OSSN).A retrospective chart review of individuals clinically diagnosed with conjunctival papilloma (n = 10) or papilliform OSSN (n = 10) based on slit lamp features. Data on demographics, tumour characteristics, and primary treatment were collected. AS-OCT features were assessed including epithelial thickness and reflectivity, a corrugated epithelial surface, presence of an overhanging edge, presence of intrinsic spaces and posterior shadowing. Histopathology was available in 5 papilloma and 3 OSSN specimens.Overall, the majority of individuals in both groups were white males. OSSN lesions were more likely to involve the limbus (80% vs.10%, p = 0.005) and the bulbar conjunctiva (100% vs. 20%, p 0.001) compared to papillomas. On AS-OCT, maximum epithelial thickness was thicker in papilloma compared to OSSN (936 ± 533 vs. 637 ± 207 µm, p = 0.009). The feature that best differentiated papilloma from OSSN was an overhanging edge (100% vs. 0%, p 0.001), where the epithelial lesion was seen on top of underlying normal epithelium. Other features more common in papilloma compared to OSSN included a corrugated epithelial surface (70% vs.10%, p = 0.02), the presence of intrinsic spaces (100% vs. 50%, p = 0.03), and posterior shadowing (100% vs. 40%, p = 0.01).AS-OCT shows differentiating features between papilloma and OSSN with an overhanging edge as a distinctive AS-OCT feature of papilloma.

To assess the effect of mask wear on corneal topography and tomography readings. Setting: Tertiary ophthalmic center. Design: Prospective, observational, comparative study.Subjects underwent imaging with the Tomey® TMS-4a topographer and the OCULUS Pentacam® HR tomographer. Imaging was performed without a mask and then testing was repeated while wearing three different masks: Halyard Level 2, Halyard Level 3 and KN95. Measurements during mask wear were compared to measurements without a mask. Kruskal-Wallis ANOVA grouped test was used to compare mean differences without vs with mask wear on measurements. Chi-square test was used to compare frequency of differences between different masks and against-the-rule versus with-the-rule astigmatism. The frequencies of clinically significant changes in axis of astigmatism, magnitude of astigmatism and mean keratometry values were calculated.52 eyes were included in the study with a mean age of 34.71. Mask wear did not show statistically significant differences in mean topography and tomography measurements compared to without mask wear for all parameters. However, the majority, 53% (83/156) had a10 degrees and 41% (64/156) had15 degrees change in axis of astigmatism on topography when wearing a mask compared to no mask wear.Mask wear did not result in statistically significant mean changes in keratometry readings on topography and tomography. However, axis of astigmatism varied10 degrees in the majority of patients. Axis determination should be interpreted with caution with respect to refractive surgery and/or toric intraocular lens planning in individuals whose measurements were obtained while wearing a mask.

PURPOSE: Optical coherence tomography angiography (OCTA) was utilized to examine changes in ocular surface squamous neoplasia (OSSN) vascular patterns over time in individuals treated with topical medical therapy. METHODS: Ten individuals with OSSN diagnosed by clinical examination and high resolution (HR)-optical coherence tomography (OCT) were recruited. All individuals received topical immuno- or chemotherapy. OCTA images were obtained and analyzed at three points: presentation, mid-treatment and tumor resolution. Tumor metrics including tumor area (TA), tumor volume (TV), tumor depth (TD), and total tumor density (TTD) were calculated. Vessel area density (VAD) was also quantified within the OSSN, the subepithelium under and adjacent to the OSSN and the subepithelium of the uninvolved, contralateral eye. Vascular network changes were also subjectively evaluated. RESULTS: TA, TV, TD and TTD all significantly decreased with time (p0.05). The mean VAD in the subepithelium adjacent to the OSSN increased with treatment, then decreased significantly between mid-treatment and resolution (23.26±4.54, 28.30±7.43% and 21.68±6.10%, p=0.009). Qualitatively, the tumor subepithelial vascular network was complex and dense but with tumor resolution appeared less tortuous and similar to the uninvolved eye. CONCLUSION: OCTA provided insight into the pathophysiology of tumor angiogenesis, showing decreased vascular density and normalization of vascular networks associated with tumor resolution.

The purpose of this study was to compare the clinical characteristics and high-resolution optical coherence tomography (HR-OCT) findings between corneal squamous metaplasia and ocular surface squamous neoplasia (OSSN).A retrospective case-control study of 8 patients, 4 with histologically confirmed squamous metaplasia and 4 with histologically confirmed OSSN, who presented to the Miami Veterans Administration Medical Center and Bascom Palmer Eye Institute between 2016 and 2020 was performed. Clinical characteristics, HR-OCT findings, and pathology were evaluated and compared.Four patients with squamous metaplasia and 4 with OSSN were evaluated. In the metaplasia group, 75% were male, 2 were White, and 2 were Black. In the OSSN group, all 4 were White males. All lesions were opalescent and occurred at the limbus; however, the borders were more smooth and rounded in the metaplastic lesions compared with OSSN. HR-OCT findings were indistinguishable between the 2 groups.There is overlap in clinical characteristics and HR-OCT findings between corneal squamous metaplasia and OSSN, highlighting one limitation of HR-OCT. As such, if a corneal opacity has some but not all HR-OCT findings of OSSN, squamous metaplasia should also be considered. A biopsy may be indicated to further evaluate and guide treatment.

PURPOSE The purpose of this study was to report the indications, ocular and systemic comorbidities, and surgical outcomes of corneal transplantation in patients older than 90 years. METHODS A retrospective review was conducted to identify individuals 90 years and older who underwent corneal transplantation surgery at the Bascom Palmer Eye Institute between January 2013 and October 2020. Outcomes included best-corrected visual acuity and graft survival over time. Paired t tests were used to compare visual acuity preoperatively versus postoperatively. Graft survival was evaluated with Kaplan-Meier curves. RESULTS Fifty-eight eyes of 52 consecutive individuals were included. The mean age of individuals was 92 ± 2 years; 26.9% were male; and 48.1% self-identified as non-Hispanic White and 38.5% as Hispanic. Postoperative follow-up was 14.7 ± 12.1 months. Of the 58 eyes, 44.8% (26/58) underwent penetrating keratoplasty, 46.6% (27/58) Descemet stripping automated endothelial keratoplasty, and 6.9% (4/58) keratoprosthesis. All surgeries were performed under monitored local anesthesia, without major complications. Surgical indications included pseudophakic bullous keratopathy (36.2%), glaucoma-associated corneal decompensation (27.6%), Fuchs endothelial dystrophy (25.9%), and perforated corneal ulceration (19.0%). The best-corrected visual acuity improved by 0.32 (95% confidence interval 0.14-0.50; P < 0.01) as early as 1 month postoperatively, and vision gains were sustained for at least 12 months. Graft survival probability at 12 months was 88%. CONCLUSIONS Corneal transplantation is a safe and successful procedure in restoring the visual acuity for patients older than 90 years after careful preoperative evaluation. Further research is needed to evaluate the impact of corneal transplantation on quality of life in patients in the 10th decade of life.

INTRODUCTION: Kaposi’s sarcoma (KS) is a multifocal low-grade vascular neoplasm that can affect the skin, mucus membranes, visceral organs, and lymph nodes. KS can also affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis. AREAS COVERED: In this review, the manifestations of ocular KS are discussed along with theories for pathogenesis, common risk factors, and management options. EXPERT OPINION: KS is caused by the oncogenic human herpesvirus 8 (HHV8). Immunosuppression in patients with HIV and AIDS contributes to the development of KS but conjunctival and ocular adnexal KS lesions are now uncommon in the era of anti-retroviral therapy. A high index of suspicion is required to diagnose ocular KS as these lesions can be mistaken for alternative entities. Prompt diagnosis can reduce significant morbidity and mortality by prompting a multidisciplinary systemic evaluation, particularly in immunosuppressed individuals. While surgical excision, cryotherapy, intralesional or systemic chemotherapy, and radiation are all viable treatment options, ongoing research to identify novel therapies and molecular treatment targets will help expand the armamentarium of therapeutics available for this disease.

The purpose of this study was to report the first case of a conjunctival granulomatous lesion as the presenting sign of granulomatous polyangiitis (GPA) in a pediatric patient.This study is a case report.A 14-year-old Hispanic boy presented with a conjunctival lesion on the inferior bulbar conjunctiva of the right eye associated with diffuse conjunctival injection. The mass progressively grew and became painful over the course of 6 weeks. No retinal or orbital abnormalities were noted on examination. The lesion was excised, and histopathological analysis was consistent with granulomatous inflammation. The lesion recurred after 15 months, and a second excisional biopsy was performed. The lesion again slowly recurred, and on presentation to our clinic, an elevated lesion in the inferior limbal/bulbar conjunctiva of the right eye was noted from 4 to 8 o'clock with accompanying forniceal shortening. Five months after the second excision, the patient developed flu-like symptoms with polyarthralgia. A full diagnostic workup revealed multiple pulmonary nodules on chest imaging, proteinuria on urinalysis, and a positive c-antineutrophil cytoplasmic antibody on serological studies. Based on these findings, the patient underwent a kidney biopsy which showed pauci-immune crescentic glomerulonephritis, consistent with a diagnosis of GPA. The patient achieved disease remission with rituximab. Despite treatment, the conjunctival lesion did not regress and remained unchanged in size for 3 years with periodic episodes of inflammation.This is the first documented case of a conjunctival mass as the initial presenting feature of pediatric GPA. The presence of granulomatous inflammation on histopathology and recurrences after excision should raise suspicion for GPA in children and adults.

Background: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. Methods: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein–protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. Results: We show that BAP1’s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1’s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value < 1.0 × 10−16). Conclusion: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm.

The aim of the study was to describe a case of Lisch epithelial corneal dystrophy (LECD), review its clinical and histopathological features and diagnostic imaging, and introduce a novel treatment approach using topical 5-fluorouracil (5-FU).A 65-year-old woman presented with a recurrent left-sided corneal lesion consistent with LECD. The lesion was evaluated clinically, with high-resolution optical coherence tomography (HR-OCT), and histologically. The lesion was successfully treated with two 1-week cycles of topical 5-FU.Slit-lamp examination showed an opalescent, whorl-shaped corneal lesion. HR-OCT revealed a trapezoidal area of normal thickness epithelial hyperreflectivity. Histopathology demonstrated a mucosal epithelium with foamy cytoplasm and increased cell size consistent with LECD. Treatment with topical 5-FU resulted in marked clearance of the corneal lesion on slit-lamp examination and HR-OCT.5-FU may be considered as a treatment option for LECD.

PURPOSE OF REVIEW: To discuss recent studies of imaging modalities for ocular surface pathologies. RECENT FINDINGS: Novel micro-ocular coherence tomography technology can produce high-resolution images of corneal cellular and nervous structures. Ocular coherence tomography angiography can aid in detecting early stage limbal stem cell deficiency. Several studies used in vivo confocal microscopy to evaluate corneal nerve metrics and morphology. SUMMARY: The applications of anterior segment optical coherence tomography, anterior segment optical coherence tomography angiography, ultrasound biomicroscopy, and in vivo confocal microscopy are useful technologies for imaging the ocular surface. Several studies have used artificial intelligence in combination with imaging technologies to create reliable and effective systems to detect and visualize ocular surface pathologies. AS OCT continues to be a key imaging tool and future development of μOCT technology may further enhance its utility.

Significance Ocular surface squamous neoplasias are superficial tumors of the cornea and conjunctiva that can be sight threatening if neglected. Therefore, accurate noninvasive diagnostic modalities are needed. Purpose The purpose of this case series was to describe the hallmark features of ocular surface squamous neoplasia on high-resolution optical coherence tomography (HR-OCT) imaging and its use in the evaluation and management of superficial ocular tumors. Case series Five eyes of four patients with ocular surface squamous neoplasia are described. Whereas two eyes displayed the classic clinical features of ocular surface squamous neoplasia, three of the five eyes had more subtle atypical features. However, all shared features on HR-OCT of epithelial thickening and hyperreflectivity with abrupt transitions between normal and abnormal tissue, classic features of ocular surface squamous neoplasia. All lesions ultimately underwent incisional or excisional biopsy and were confirmed to be ocular surface squamous neoplasia on histopathology. Conclusions Ocular surface squamous neoplasia may present as a classic tumor but can also have subtle features or masquerade. Accurate methods to diagnose and manage patients with ocular surface squamous neoplasia are necessary. With recent advancements in technology, HR-OCT has been demonstrated to accurately identify ocular surface squamous neoplasia with the repeatable optical findings of (1) epithelial thickening, (2) epithelial hyperreflectivity, and (3) abrupt transition zone between normal and abnormal tissue. This case series demonstrates how HR-OCT can help provide an optical biopsy to guide appropriate diagnosis and management of this neoplastic lesion.

PURPOSE: To characterize retinal neurovasculature changes after small-incision lenticule extraction (SMILE) in myopic patients. SETTING: Ophthalmic Center, the Second Affiliated Hospital of Guangzhou Medical University, China. DESIGN: Prospective interventional study. METHODS: The corrected distance visual acuity/uncorrected distance visual acuity, corrected intraocular pressure (CIOP), and corneal tomography were evaluated at baseline (PRE), postoperative day (POD) 1, and POD 7. Ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were measured. The vessel area densities (VADs, %), vessel skeleton densities (VSDs, %), vessel diameter index (VDI), and fractal dimensions (Dbox) of the superficial vascular plexus (SVP) and deep vascular plexus (DVP) were measured in a circular area (ϕ 2.5 mm) centered on the fovea. RESULTS: A total of 38 myopic patients were recruited. The GCIPL thickness was increased after SMILE at POD 1 and POD 7 (P < .01) but no significant changes in the pRNFL thickness. The VAD, VSD, and Dbox of the SVP were decreased at POD 1 (P < .01), but not at POD 7. The VDI in small vessels of the SVP and DVP was decreased at POD 1 (P < .05) and increased at POD 7 (P < .05). Changes in CIOP were positively correlated with changes in the GCIPL thickness. Changes in CIOP were negatively correlated with changes in the VAD of small vessels and the Dbox of total vessels in the DVP. Changes in CIOP were negatively correlated with the VSD and VDI of small vessels in the DVP and changes in the VDI of big vessels in the SVP. CONCLUSIONS: The transient fluctuations in the retinal neurovasculature after SMILE may represent a characteristic homeostasis pattern in patients after refractive surgery.

Purpose To report the unexpected finding of ocular surface neoplasia (OSSN) on conjunctival tissue removed during pterygium surgery and subjected to histopathology analysis. Methods This is an observational, descriptive retrospective study in which all the samples removed during surgery between 1997 and 2020 with a clinical diagnosis of pterygium were sent for histopathology analysis in which an unexpected OSSN was found. Results There were 461 cases with a preoperative diagnosis of pterygium, with a mean age of 30.14 ± 10.6 years. In this group, there was an unexpected finding of OSSN in 69 cases (14.96%) of the surgical samples, with a mean age of 46 ± 8.2 years (31.86 ± 12.13). Conclusions The unexpected coincidence of pterygium and OSSN is frequent, although varies depending on the geographical location. We recommend performing a histopathology analysis on every pterygium removed.

PURPOSE This study characterized ocular pain symptoms in individuals with and without a history of refractive surgery (RS) using a cross-sectional survey of individuals with ocular pain. METHODS A link to an anonymous survey was posted on a corneal neuralgia Facebook group that included individuals with ocular pain from any etiology and sent to individuals seen in our clinic with ocular pain. The survey asked about medical history, ocular pain symptoms (using standardized questionnaires), and treatment responses. Respondents were split into 2 groups based on a history of RS. RESULTS One hundred one individuals responded to the survey. The mean age for all respondents was 41.6 ± 15.6 years, and 50% reported a history of RS. A total of 46% of individuals with a history of RS reported that their ocular pain started within 1 month of surgery, with median pain duration of 36 (interquartile range 22-84) months. The median Dry Eye Questionnaire-5 (range 0-22) scores were 16 and 15 for the RS and no-RS groups, respectively. Most individuals in both groups characterized their pain as burning (score ≥1: RS, 86%; no-RS, 80%) and reported evoked pain to wind, light, or temperature (score ≥1: RS, 97%; no-RS, 85%). Fifty-nine of 101 individuals responded to treatment questions. Individuals in both groups reported >30% improvement in pain symptoms with some topical and systemic approaches. CONCLUSIONS Individuals with a history of RS developed ocular pain soon after surgery, which persisted for years. Symptom profiles were similar between those with and without RS. Topical and systemic approaches can treat pain in both groups.

In recent years, there has been tremendous enthusiasm with respect to detailing the genetic basis of many neoplasms, including conjunctival melanoma (CM). We aim to analyze five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN. We evaluated each protein for its intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI) with the Predictor of Natural Disordered Protein Regions (PONDR®) and the Search Tool for the Retrieval of Interacting Genes (STRING®). Our PONDR® analysis found high levels of IDPRs in all five proteins with mutations linked to CM. The highest levels of IDPRs were in BRAF (45.95%), followed by PTEN (31.76%), NF1 (22.19%), c-KIT (21.82%), and NRAS (14.81%). Our STRING analysis found that each of these five proteins had more predicted interactions then expected (p-value &lt, 1.0 × 10−16). Our analysis demonstrates that the mutations linked to CM likely affected IDPRs and possibly altered their highly complex PPIs. Quantifying IDPRs in BRAF, NRAS, c-KIT, NF1, and PTEN and understanding these protein regions are important processes as IDPRs can be possible drug targets for novel targeted therapies for treating CM.

The purpose of this study was to report a unique case of ocular surface squamous neoplasia that masqueraded as a nonresolving toxic epithelial keratitis.This was a case report and review of the literature.A 79-year-old man presented with decreased vision, redness, and a foreign body sensation in his right eye that was refractory to treatment with lubrication and topical nonsteroidal antiinflammatory drops. Before presentation, the referring provider believed that he had medicamentosa-related keratitis and placed him on oral methazolamide. Slitlamp biomicroscopy of the right eye revealed diffuse epitheliopathy with punctate fluorescein staining and subtle underlying corneal epithelial opalescence. A mildly thickened and inflamed pinguecula was noted from 2 to 5 o'clock at the limbus of the right eye. An anterior segment high-resolution optical coherence tomography revealed thickened, hyperreflective epithelium with an abrupt transition. An incisional biopsy confirmed conjunctival and corneal intraepithelial neoplasia. The patient improved after 4 cycles of topical chemotherapy with 1% 5-fluorouracil eye drops with complete resolution of the corneal and conjunctival pathology.Ocular surface squamous neoplasia can rarely masquerade as a recalcitrant medicamentosa and epithelial keratitis. In subtle cases or in cases with combined ocular surface morbidities, anterior segment high-resolution optical coherence tomography can be helpful to diagnose and direct therapy.

INTRODUCTION: Ocular surface masqueraders encompass any ocular surface lesion masquerading as another ocular surface lesion. High resolution optical coherence tomography (HR-OCT) has emerged as an adjunctive tool to clinical acumen. This study’s purpose is to evaluate the utility of HR-OCT images in guiding the diagnosis and management of those lesions. MATERIAL AND METHODS: 22 individuals with a clinically ambiguous ocular surface lesion with slit lamp photographs (SLP), HR-OCT images, and histopathological examination were included in the study. The presumptive clinical diagnosis based on SLP was compared to the diagnosis suggested by HR-OCT findings and to definitive diagnosis by histopathology. The main outcome of this study was the frequency in which HR-OCT findings guided the clinician to the correct diagnosis. RESULTS: 7 lesions were epithelial, 3 had an epithelial and a subepithelial component, and 12 were subepithelial. HR-OCT was most effective in discerning lesion location, successfully identifying the location in 100% of cases. Classic HR-OCT findings were detected in 68.2% of cases while suggestive features were detected in 31.8% of cases. The epithelial lesions’ mean epithelial thickness was 265.4±140.6 μm, the subepithelial lesions’ mean was 58.0±25.0 μm, and the combined lesions’ mean was 140.0±70.0 ±m. The epithelium was significantly thicker in epithelial lesions compared to subepithelial and combined lesions. By ROC analysis we identified that using a cut off of 156 μm, the sensitivity was 86% and the specificity was 93%. DISCUSSION: HR-OCT can be a valuable diagnostic tool, assisting in the differentiation of ambiguous ocular surface pathologies by providing a cross-sectional, morphological image of the lesion.

Purpose This review will summarize the clinical and histological presentation of Salzmann nodular degeneration (SND), its prevalence and risk factors, potential underlying mechanisms, diagnostic tools, management options, and impact on cataract surgery and co-morbid ocular surface diseases. Method PubMed review of 44 articles published between 1976 and 2018. Results SND is a corneal disease characterized by whitish gray or bluish nodules on the peripheral or central cornea. The clinical presentation of SND is variable and the nodules can be asymptomatic or cause foreign body sensation and/or blurred vision. Histologically, SND appears as subepithelial nodules with thin overlying epithelium, disrupted or absent Bowman's layer, and activated fibroblasts within the nodule. SND pathogenesis is not fully understood but is thought to involve poor epithelial protection and disruption of the epithelial-stromal interface, allowing for penetration of epithelially derived growth factors into the stroma and subsequent activation of stromal fibroblasts, eventually leading to sub-epithelial deposition of disorganized extracellular membrane components. SND most commonly occurs in Caucasian females in a bimodal distribution, occurring in the fifth or eighth and ninth decades of life. Risk factors for SND include ocular surface diseases and surgery. Surgical intervention is recommended in individuals with symptomatic nodules - primarily superficial keratectomy performed with or without intraoperative mitomycin C, photokeratectomy, and/or amniotic membrane transplantation. These procedures have been successful in removing the lesion and reducing corneal irregularity, but have variable recurrence rates (0-31%). Conclusion The pathogenesis of SND is complex and multifactorial. Advances in diagnostic and treatment modalities have allowed for earlier and more accurate diagnosis and effective treatment of SND.

Purpose of review This review will discuss the utility of high-resolution anterior segment optical coherence tomography (HR-OCT), in-vivo confocal microscopy (IVCM) and ultrasound biomicroscopy (UBM) in characterizing and diagnosing various ocular surface tumors, namely ocular surface squamous neoplasia (OSSN), conjunctival lymphoma and conjunctival melanoma. The strengths and limitations of each imaging modality will be discussed along with the characteristics findings of each lesion on each imaging platform. Recent findings HR-OCT can consistently be utilized in the clinic setting to distinguish between epithelial ocular surface tumors such as OSSN as compared with subepithelial tumors such as conjunctival lymphoma and conjunctival melanoma given their distinctive findings. IVCM can be used as an adjunct to HR-OCT to obtain cellular and surface characteristics, whereas UBM can be used to assess tumor depth and thickness for larger and highly pigmented lesions as well as to detect intraocular invasion. Summary HR-OCT, IVCM and UBM are all helpful imaging modalities to diagnose and characterize various ocular surface tumors and can serve as valuable adjuncts to monitor treatment response and assess for recurrence ocular surface tumors.

Mutations in the titin (TTN) gene are among the most common genomic aberrations in ocular surface squamous neoplasia (OSSN), the most common cancer of the external eye. Further, TTN mutations are associated with resistance to standard therapy with topical interferon alpha-2b (IFN-α2b). However, it remains unclear how TTN mutations drive OSSN pathogenesis and treatment resistance. TTN encodes the largest protein in the human body and its best understood function is as a myofibril scaffold in striated muscle. However, recent evidence indicates that TTN has additional functions in non-muscle cells and in cancer. Here, we performed a disorder-based bioinformatics analysis which revealed that intrinsically disordered protein regions are abundant in TTN and provide mechanistic insights into its function as a nuclear protein in epithelial cells. Specific mutations found in OSSN are predicted to affect its intrinsically disordered protein regions (IDPRs), promoting chromosomal instability, oncogenesis, and altered response to IFN-α2b treatment.

INTRODUCTION: High resolution anterior segment optical coherence tomography (HR-OCT) has revolutionized the way by which clinicians can diagnose and differentiate ocular surface lesions. Careful interpretation of HR-OCT images can provide morphological information about the lesion of interest and help guide the diagnosis. AREAS COVERED: This paper reviews the steps to interpreting HR-OCT images of ocular surface lesions and summarizes their characteristic findings. EXPERT OPINION: Among the multiple modalities available to image the ocular surface and anterior segment, HR-OCT has emerged as an instrumental tool to obtain “optical biopsies” of various ocular surface lesions. A step-by-step approach to acquiring and interpreting HR-OCT images can allow for accurate in-office characterization and diagnosis of both benign and malignant ocular surface lesions.

Purpose To present a rare presentation of pyogenic granuloma arising almost 4 decades after a scleral buckle for retinal detachment. Method We describe the clinical presentation, diagnostic workup, and management of a suspicious conjunctival lesion in an immunocompromised patient. We report the histopathological findings and the postoperative outcome. Results A 58-year-old man with human immunodeficiency virus presented for evaluation of a possible malignant conjunctival lesion in the left eye. The patient reported that the lesion had appeared 1.5 months before presentation with significant growth over the past month. The patient denied any trauma to the eye other than an ocular history of retinal detachment repair with scleral buckle 37 years earlier. Clinical examination revealed a pink, fleshy, mobile, and lobulated conjunctival lesion measuring 7 mm by 10 mm, emanating from the superior-nasal bulbar quadrant. A high-resolution optical coherence tomography revealed highly cellular infiltrate and hyperreflective mass with significant posterior shadowing. Further exploration of the lesion revealed a white, stringy, cauliflower-like material on the underside of the lesion. Surgical excision and pathology subsequently confirmed a diagnosis of pyogenic granuloma with remnants of silk suture. Conclusions A diagnosis of pyogenic granuloma secondary to retained silk sutures should be considered in patients with a history of intraocular surgery irrespective of other risk factors and length of time since procedure.

Anterior segment high-resolution optical coherence tomography (HR-OCT) plays a pivotal role in the diagnosis of corneal and conjunctival lesions. Ocular surface squamous neoplasia (OSSN), the most common non-pigmented neoplasia of squamous cell origin, has variable appearances which include leukoplakic, papillary, opalescent, and gelatinous presentations. Pigmented lesions entail a lengthy differential, ranging from benign cystic nevi to life-threatening melanomas. The establishment of classic findings of OSSN and other ocular surface lesions on HR-OCT has greatly facilitated the identification of ocular surface pathologies. This chapter serves to outline the characteristic findings attributable to the following ocular surface lesions: ocular surface squamous neoplasia (OSSN), Salzmann’s nodule, pterygium, sebaceous carcinoma, papilloma, lymphoma, amyloid, nevus, melanoma, primary acquired melanosis (PAM), complexion-associated melanosis (CAM), and inclusion cyst. HR-OCT provides morphological views of the lesions that greatly aid in diagnosis, in guiding therapy to full resolution, in detecting early recurrence, and in detecting residual postoperative disease in surgical cases.

PURPOSE To compare the endothelial cell density (ECD) and quality of corneal grafts from young donors who sustained airbag deployment in motor vehicle accidents (MVA) or gunshot wounds (GSW) to the head with grafts from donors of similar age who died of other causes. METHODS This is a retrospective comparative series of 65 corneal grafts from 33 young donors (mean age, 29.60 ± 8.95 yrs), with the cause of death either MVA with airbag deployment (n = 7), GSW to the head (n = 14), or other nontrauma-related cause (n = 12). Donor characteristics, graft quality on slit-lamp examination, ECD, and areas of endothelial cell loss on specular microscopy were compared between the groups. RESULTS Donor age, graft quality on slit-lamp examination, and death-to-preservation time were similar between the groups. Statistically significant differences in focal areas of endothelial cell loss were found in the MVA- and GSW-derived grafts compared with the nontrauma-related grafts (85.7% vs. 0%, P value 0.0002 and 92.5% vs. 0%, P value

Purpose To determine genetic mutational profiles in patients with Ocular Surface Squamous Neoplasia (OSSN) using whole exome sequencing. Methods Prospective, case-series study. Patient recruitment was conducted in a single tertiary referral center from April to September 2017. Specimens were obtained by incisional biopsies of tumors from ten eyes with histopathologic confirmation of OSSN. DNA whole exome sequencing and mutation analysis were performed. Results Ten patients with clinically-diagnosed OSSN underwent DNA whole exome sequencing analysis. Deleterious mutations in 305 genes known to drive tumor development and progression were found. These mutations centered around two main pathways: DNA repair/cell cycle and development/growth. All ten samples had at least one mutation in a DNA repair/cell cycle gene and all but one sample had one in a development/growth gene. The most common mutation was found in TP53 and HGF (both present in 50% of cases) and mutually exclusive mutations were found in BRCA1 and BRCA2 (50% of cases). Mutations in APC, MSH6, PDGFRA, and PTCH1 were found in 40% of cases. Global mutation analysis identified ultraviolet induced radiation as the only mutational signature present in the dataset. Conclusions Mutations found in samples from patients with OSSN are mainly induced by ultraviolet radiation and occur within two main pathways related to DNA repair/cell cycle and development/growth. There are many clinically available drugs and several others being evaluated in clinical trials that target the genes found mutated in this study, offering new therapeutic options for OSSN.

Objective The aim of the study is to report the creation of a flipped ophthalmology course and preclinical medical student perceptions and knowledge gains before and after a flipped ophthalmology course. Design The form of the study discussed is an observational study. Subjects The subjects involved in the study are second-year (U.S.) United States medical students at the University of Miami, Miller School of Medicine (n = 401). Methods Second-year medical students participated in a 1-week “flipped classroom” ophthalmology course geared toward primary care providers at the University of Miami, Miller School of Medicine. Eleven hours of traditional classroom lectures were condensed into 4.5 hours of short videos with self-assessment quizzes, small group discussions, and a large group case-based discussion. Fifty-seven short videos ( Main Outcome Measures The main outcome measures include: student final exam performance; student satisfaction, opinions, and perceptions. Results Over the course of 2 years, 401 second-year U.S. medical students participated in the flipped classroom ophthalmology course. The majority of students enjoyed the flipped classroom experience (75.3%) and expressed interest in using the approach for future lessons (74.6%). The flipped classroom videos were preferred to live lectures (61.2%). Over 90% of students stated the self-assessment quizzes were useful, 79% reported that the small group discussions were an effective way to apply knowledge, and 76% cited the large group case-based discussion as useful. Pre-course knowledge assessment scores averaged 48%. Final examination scores in the flipped group (average ± standard deviation [SD] = 92.1% ± 6.1) were comparable to that of the traditional group when evaluating identical questions (average ± SD = 91.7% ± 5.54), p = 0.34. Conclusion The flipped classroom approach proved to be a well-received and successful approach to preclinical medical education for ophthalmology. This was achieved using 35% less course time than our traditional course. This innovative approach has potential for expansion to other medical schools, medical education abroad, and for other medical school modules.

Purpose To characterize vision-related and psychosocial quality of life (QoL) parameters in medically and surgically treated patients with OSSN. Methods Forty-one patients with OSSN treated with medical therapy consisting of interferon alpha 2b drops 1 MIU/ml (n = 22) or who underwent surgical excision (n = 19) were contacted. All subjects answered a quality of life assessment with an original questionnaire in which they were asked about a range of parameters. Overall satisfaction and motivating factors for treatment were also reviewed. Results The mean age at the time of the survey was 64.6 and 51% were male with similar demographics between groups. Based on the previous cohort, rates of tumor resolution and recurrences were comparable in the two groups. Reasons for choosing a particular treatment varied between the groups. Forty percent of individuals in the medical group reported a fear of surgery (p = 0.03) and often made the decision after personal research (p = 0.008). Thirty-two percent of patients in the surgical group chose surgery due to fear of decreased vision due to lesion growth, therefore wanting immediate resolution (p = 0.09). Drops precipitated more ocular symptoms such as tearing and itchiness, on the other hand, patients who had surgery reported having more pain. Conclusion Quality of life considerations before, during, and after OSSN treatment is an important yet understudied topic. Our study is the first to look at QoL parameters in OSSN treatment and we found that patients in both medically and surgically treated groups had similar QoL metric but were driven to choose chemotherapy due to fear of surgery and/or prior literature review.