Medical treatment for ocular surface squamous neoplasia.

Ocular surface squamous neoplasia (OSSN) is the most common non-melanocytic tumour of the ocular surface. Surgical excision with wide margins using the "no-touch" method was originally the most popular treatment for OSSN. However, in the past two decades, the use of topical medications for OSSN treatment has gained a reputation amongst ophthalmologists for being an effective alternative to surgical excision. Furthermore, technological advancements, such as those seen in high-resolution optical coherence tomography (HR-OCT) for the anterior segment, have facilitated the diagnosis and monitoring of OSSN. When selecting a topical agent, interferon alpha-2b (IFNα-2b) and 5-fluorouracil (5-FU) are two of the gentlest medications used for OSSN and are often considered first line therapies due to their high-resolution rates and mild side effect profiles. Mitomycin C (MMC), on the other hand, has a highly toxic profile; therefore, while effective, in our hands it is considered as a second-line treatment for OSSN if the other modalities fail. In addition, newer and less studied agents, such as immune checkpoint inhibitors, retinoic acid, aloe vera, and anti-vascular endothelial growth factor have anti-neoplastic properties and have shown potential for the treatment of OSSN. We enclose an updated literature review of medical treatments for OSSN.

A comparative review of evaporative dry eye disease and meibomian gland dysfunction in dogs and humans.

Dry eye disease is a complex ophthalmic disorder that consists of two main subtypes, aqueous deficient dry eye (ADDE) and evaporative dry eye disease (EDED). Due to the complex underlying physiology, human dry eye disease can be difficult to model in laboratory animal species. Thus, the identification and characterization of a spontaneous large animal model of dry eye disease is desirable. Dogs have been described as an ideal spontaneous model of ADDE due to the similar pathophysiology between dogs and humans. Recently, EDED and meibomian gland dysfunction (MGD) have been increasingly recognized and reported in dogs. These reports on EDED and MGD in dogs have identified similarities in pathophysiology, clinical presentations, and diagnostic parameters to humans with the comparable disorders. Additionally, the tests that are used to diagnose EDED and MGD in humans are more easily applicable to dogs than to laboratory species due to the comparable globe sizes between dogs and humans. The reported response of dogs to EDED and MGD therapies are similar to humans, suggesting that they would be a valuable preclinical model for the development of additional therapeutics. Further research and clinical awareness of EDED and MGD in dogs would increase their ability to be utilized as a preclinical model, improving the positive predictive value of therapeutics for EDED and MGD in both humans and dogs.

Conjunctival papilloma treatment outcomes: a 12-year-retrospective study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Papilloma resolution is faster with surgical excision as compared to medical therapy. However, recurrences are more frequent after surgical versus medical treatment.

Fecal Microbial Transplant in Individuals With Immune-Mediated Dry Eye.

PURPOSE: To evaluate the safety of the Fecal Microbial Transplant for Sjogren Syndrome (FMT) trial in individuals with immune-mediated dry eye (DE). DESIGN: Open-label, nonrandomized clinical trial. METHODS: The study population included 10 individuals with DE symptoms and signs meeting criteria for Sjögren or positive early Sjögren markers. Procedures were 2 FMTs from a single healthy donor delivered via enema, 1 week apart. The primary outcome measure was safety. In addition, gut microbiome profiles, DE metrics, and T-cell profiles in blood were examined at baseline before FMT, and at 1 week, 1 month, and 3 months after FMT. RESULTS: The mean age of the population was 60.4 years; 30% were male; 50% were white; and 50% were Hispanic. At baseline, all subjects had significantly different gut microbiome profiles from the donor, including higher mean diversity indices. Subjects had a decreased abundance of genera Faecalibacterium, Prevotella, and Ruminococcus and an increased abundance of genera Alistipes, Streptococcus, and Blautia compared to the donor. Effector and regulatory T-cell profiles were positively correlated with each other and with DE symptom severity (T helper 1 cells [Th1]; r = .76; P = .01; Th17: r = 0.83; P = .003; CD25: r = 0.66; P = .04; FoxP3: r = 0.68; P = .03). No adverse events were noted with FMT. After FMT, gut microbiome profiles in 8 subjects moved closer to the donor's profile. As a group, gut microbiome profiles at all follow-up time points were more similar to the original recipients' than the donor's microbiome; however, certain phyla, classes, and genera operational taxonomic unit (OTU) numbers remained closer to the donor vs recipients' baseline profiles out to 3 months. Five individuals subjectively reported improved dry eye symptoms 3 months after FMT. CONCLUSIONS: FMT was safely performed in individuals with immune-mediated DE, with certain bacterial profiles resembling the donor out to 3 months after FMT. One-half the subjects reported improved DE symptoms. The most effective FMT administration method has yet to be determined.

Alternative therapies for dry eye disease.

PURPOSE OF REVIEW: Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited to, lacrimal gland hypofunction, meibomian gland dysfunction (MGD), ocular surface inflammation, and corneal nerve dysfunction. Current DED treatments target some facets of the disease, such as ocular surface inflammation, but not all individuals experience adequate symptom relief. As such, this review focuses on alternative and adjunct approaches that are being explored to target underlying contributors to DED. RECENT FINDINGS: Neuromodulation, stem cell treatments, and oral royal jelly have all been studied in individuals with DED and lacrimal gland hypofunction, with promising results. In individuals with MGD, devices that provide eyelid warming or intense pulsed light therapy may reduce DED symptoms and signs, as may topical Manuka honey. For those with ocular surface inflammation, naturally derived anti-inflammatory agents may be helpful, with the compound trehalose being farthest along in the process of investigation. Nerve growth factor, blood-derived products, corneal neurotization, and to a lesser degree, fatty acids have been studied in individuals with DED and neurotrophic keratitis (i.e. corneal nerve hyposensitivity). Various adjuvant therapies have been investigated in individuals with DED with neuropathic pain (i.e. corneal nerve hypersensitivity) including nerve blocks, neurostimulation, botulinum toxin, and acupuncture, although study numbers and design are generally weaker than for the other DED sub-types. SUMMARY: Several alternatives and adjunct DED therapies are being investigated that target various aspects of disease. For many, more robust studies are required to assess their sustainability and applicability.

Long-Term Trigeminal Nerve Stimulation as a Treatment for Ocular Pain.

OBJECTIVES: Ocular pain symptoms (e.g., hypersensitivity to light and wind, "burning" sensations) can be debilitating and difficult to treat. Neuromodulatory therapies targeting sensory trigeminal and central pain pathways may help treat chronic ocular pain refractory to traditional therapies. The current study evaluates the long-term effects of a trigeminal neurostimulator (TNS) on ocular pain. MATERIALS AND METHODS: Retrospective review of 18 individuals at the Miami Veterans Affairs Eye Clinic with chronic, severe ocular pain who were prescribed and used TNS at home for ≥3 months. The primary outcome measures were 1) ocular symptom intensity over a 24-hour recall period (dryness, pain, light sensitivity, wind sensitivity, burning; rated on 0-10 scales) captured pre-TNS and at monthly follow-up intervals and 2) side effects. The frequency and duration of TNS was a secondary outcome measure. RESULTS: The mean age of the population (n = 18) was 57.5 years (range, 34-85 years) with a male majority (67%). Two individuals discontinued use due to lack of efficacy and one due to confounding health issues. Initial mean weekly frequency of TNS use was 3.7 ± 1.9 sessions of 25.8 min at month 1 and 2.7 ± 2.3 sessions of 28.0 min at month 6. At six months, pain intensity (↓ 31.4%), light sensitivity (↓ 36.3%), wind sensitivity (↓ 32.6%), and burning sensation (↓ 53.9%) were all decreased compared to baseline (p < 0.01 for all); greater decreases in ocular pain were noted in individuals with migraine (n = 10) than those without migraine (n = 8). No significant change was noted in mean dryness scores. Fifteen subjects experienced sedation with TNS use, persisting throughout the follow-up visits. No other adverse effects were communicated by any subjects. CONCLUSION: Our study suggests TNS is a safe, adjunctive treatment option in individuals with severe, chronic ocular pain. Individuals demonstrated gradual, continual improvement in pain symptoms over time within a multimodal approach.

Transcutaneous Electrical Nerve Stimulation for Facial Pain.

Transcutaneous electrical nerve stimulation (TENS) has been used for its analgesic effects for chronic pain, including facial pain. Here, we summarize how the electrical stimulation of branches of the trigeminal nerve via TENS has been utilized to reduce pain resulting from trigeminal neuralgia, temporomandibular joint disorder, migraine and other headache types, and ocular pain sensations. TENS has been used for both short-term (one session) and long-term (multiple sessions) pain control with little to no adverse effects reported by subjects. The results of the summarized studies suggest TENS is an effective non-invasive, non-pharmacologic means of pain control for patients with facial pain conditions.

Transcutaneous Electrical Nerve Stimulation for the Long-Term Treatment of Ocular Pain.

PURPOSE: Ocular pain is a debilitating condition that is challenging to treat as therapies that target the ocular surface are often ineffective. We previously reported a short-term reduction in ocular pain after one periocular transcutaneous electrical nerve stimulation (TENS) session. The current study aims to elucidate the long-term effect of TENS on ocular pain. MATERIALS AND METHODS: Fourteen individuals with eye pain were identified as candidates for a TENS device (RS Medical, Vancouver) for home use after a successful trial in clinic between February 2018 and July 2019 at the Miami Veterans Administration Hospital or University of Miami. Ten of the 14 patients were included in this retrospective review, based on the inclusion of receiving and using the device for a minimum of three months. The median age of the ten patients was 47.5 years, range 32-73 years, and eight were male. The main outcome measures were 1) frequency of long-term integration of TENS into ocular pain management and 2) patient reported ocular pain intensity (0-10) pre- vs. post-treatment. RESULTS: Patients reported an initial median use of the device 14.0 times per week and over time reducing the frequency to 3.0 times per week. All reported that the TENS unit was successfully incorporated into their ocular pain management routine for at least three months (median duration of use 6.5 months, range 3-14 months). Nine of ten patients reported subjective pain reduction with use of the TENS device at home. Overall, pain intensity decreased by approximately 27.4% (mean rank = 5.6, Z = -2.1, p = 0.02) post- vs. pre-treatment. No adverse events associated with TENS were reported in any patient. CONCLUSION: Our preliminary data suggest that TENS can be integrated into the long-term management of ocular pain with improvements in overall pain intensity.

Effect of non-invasive intranasal neurostimulation on tear volume, dryness and ocular pain.

PURPOSE: To evaluate the effect of one TrueTear session on change in tear volume and symptoms of dryness and ocular pain. METHODS: Retrospective interventional case series of patients seen in a dry eye clinic. Seventy-five individuals underwent an ocular surface examination and one session of neurostimulation. Outcome measures included objective change in tear volume measured via phenol red test, and subjective change in sensations of dryness and ocular pain measured on a 0-10 Numerical Rating Scale. RESULTS: The mean age of the 75 individuals was 59±13 years, and the majority were male (73%). Intranasal neurostimulation increased tear volume (mean 13.40±8.00 mm, p<0.0005) and reduced intensities of dryness (mean -2.85±2.79, p<0.0005) and ocular pain (mean -1.48±2.41, p<0.0005 for both). However, these effects were independent of one another as change in symptom report did not correlate with change in tear volume (r=-0.13, p=0.25 for dryness; r=0.07, p=0.56 for pain). In a multivariable model, the strongest predictors for increased tear volume were lower baseline tear volume (standardised beta (ß)=-0.50, p<0.0005) and absence of an autoimmune disease (ß=-0.36, p=0.001) (R2=0.30). The strongest predictors for reduced dryness and pain scores were lower baseline dryness and ocular pain scores. No complications related to neurostimulation were noted. CONCLUSION: Intranasal neurostimulation increased tear volume and reduced intensities of dryness and ocular pain, independently of one another.

Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study.

PURPOSE: To report clinical outcomes of rose bengal photodynamic antimicrobial therapy (RB-PDAT) as an adjunct treatment for severe, progressive infectious keratitis. DESIGN: Consecutive interventional case series. METHODS: Patients with progressive infectious keratitis unresponsive to standard medical therapy underwent RB-PDAT at the Bascom Palmer Eye Institute from January 2016 through March 2018. RB-PDAT was performed by applying a solution of rose bengal (0.1% or 0.2% RB in balanced salt solution) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm2 custom-made green LED source for 15 minutes (5.4 J/cm2). RESULTS: The current study included 18 patients (7 male and 11 female) ranging from 17 to 83 years old. Acanthamoeba was the most frequent microbe (10/17; 59%), followed by Fusarium spp. (4/17; 24%), Pseudomonas aeruginosa (2/17; 12%), and Curvularia spp. (1/17; 6%); 1 patient had no confirmed microbiologic diagnosis. Main clinical risk factor for keratitis included contact lens wear (79%). The average area of epithelial defect prior to first RB-PDAT was 32 ± 27 mm2 and average stromal depth hyperreflectivity measured with anterior segment optical coherence tomography was 269 ± 75 µm. Successful RB-PDAT (avoidance of therapeutic keratoplasty) was achieved in 72% of the cases, with an average time to clinical resolution (decreased pain and inflammation with re-epithelialization and infiltrate resolution) of 46.9 ± 26.4 days after RB-PDAT. Time of follow-up after RB-PDAT was 13.3 ± 5.7 months. CONCLUSION: RB-PDAT can be considered as an adjunct therapy for cases of severe, progressive infectious keratitis before performing a therapeutic keratoplasty.

Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia.

INTRODUCTION: "Dry eye" or "keratoconjunctivitis sicca" is a multifactorial disease estimated to have a worldwide prevalence of 5-33%. Conventional therapies targeting the ocular surface with artificial tears, anti-inflammatories, punctal closure, eyelid hygiene, and antibiotics do not provide relief in all patients, especially those with neuropathic-like ocular complaints (wind hyperalgesia and photophobia). We anticipated that ocular transcutaneous electrical nerve stimulation (TENS) would alleviate symptoms of ocular pain, photophobia, and dryness in these latter individuals. METHODS: All individuals who received electrical stimulation between May 10, 2016 and April 6, 2017 for the treatment of chronic ocular pain at the oculofacial pain clinic of the Miami Veterans Administration Hospital were included in this retrospective review. All patients had symptoms of dryness along with other neuropathic-like symptoms (e.g., photophobia) and minimal signs of tear dysfunction. Ocular pain intensity, symptoms of dryness, and light sensitivity were compared pre-treatment and five min post-treatment via a two-tailed paired Student's t-test. RESULTS: The use of TENS significantly reduced the mean pain intensity in both the right and left eyes five min after treatment compared to prior to treatment (p < 0.05, paired t-test). The use of TENS significantly decreased light sensitivity in both eyes (p < 0.05). The findings for symptoms of dryness, however, were equivocal with a significant decrease in the left eye but not the right (p < 0.05, paired t-test). DISCUSSION: Our data indicate that TENS may similarly provide analgesia in patients with dry eye symptoms as it does for many other chronic pain conditions. Furthermore, the noted effect on symptoms of photophobia and dryness suggest that all may be linked by similar trigeminal-thalamic-cortical pathways. Prospective studies with electrical stimulation of dry eye are needed to further elucidate its benefit and mechanism of action.

Evidence of central sensitisation in those with dry eye symptoms and neuropathic-like ocular pain complaints: incomplete response to topical anaesthesia and generalised heightened sensitivity to evoked pain.

OBJECTIVE: To evaluate how closely neuropathic-like ocular pain (NOP) symptoms align with a metric of central sensitisation (ie, the presence of persistent ocular pain after topical anaesthetic placement) in individuals with dry eye (DE) symptoms. DESIGN: Cross-sectional study of 224 individuals with DE symptoms seen in the Miami Veterans Affairs eye clinic. An evaluation was performed consisting of questionnaires regarding DE symptoms, NOP descriptors and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Subsequent analyses were performed to examine for differences between those with and without ocular pain after topical anaesthetic placement. RESULTS: The mean age was 62 years with 91% being men. DE symptoms and NOP symptoms were higher in subjects with persistent ocular pain after anaesthesia. Most DE signs were not related to persistent pain, with the exception of meibum quality. Individuals with persistent ocular pain also demonstrated greater sensitivity to evoked pain at testing sites on the forehead and forearm. When examining receiver operator characteristic curves considering persistent pain as a gold standard for central sensitisation within the corneal pathway, intensity of ocular pain ratings, Ocular Surface Disease Index scores and sensitivity to light provided the most robust relationships, each with an area under the curve of 0.72. CONCLUSIONS: Individuals with DE symptoms and persistent ocular pain after topical proparacaine (a marker of central sensitisation to pain) more frequently report NOP-like symptoms and demonstrate increased sensitivity to evoked pain.

Compliance and Subjective Patient Responses to Eyelid Hygiene.

OBJECTIVES: Lid hygiene is a commonly prescribed first-line therapy in patients with lid margin disease, yet compliance with therapy is not well characterized. The goals of this study were to assess patient compliance with lid hygiene and evaluate which factors predict a favorable symptomatic response to treatment. METHODS: This was a cross-sectional study of patients seen in the Miami Veterans Affairs eye clinic between August and December 2014. An evaluation was performed to assess dry eye symptoms and lid margin signs. All patients were then instructed to perform warm compresses and lid scrubs. A follow-up phone survey assessed compliance and subjective therapeutic response 6 weeks later. RESULTS: Two hundred seven of 211 (98%) patients (94% male, 60% white) completed the survey. Of the 207 patients, 188 (91%) completed the follow-up survey. Compliance with therapy was reported in 104 patients (55%); 66 reported complete improvement, 30 partial improvement, and 8 no improvement in symptoms. Patients who self-reported dry eye symptoms at first visit (n=86, 74%) were more likely to be compliant with lid hygiene than those who did not report symptoms (n=18, 25%) (P<0.0005). The only factor associated with poorer response to lid hygiene was longer time of self-reported dry eye symptoms. None of the other signs studied, including the presence of skin rosacea and lid margin telangiectasia, were associated with a differential response to lid hygiene. CONCLUSIONS: Patients with dry eye symptoms were moderately compliant with lid hygiene, and patients who performed the routine noted improvement in symptoms.

ω-3 Tear Film Lipids Correlate With Clinical Measures of Dry Eye.

PURPOSE: ω-3 and ω-6 polyunsaturated fatty acids modulate inflammatory processes throughout the body through distinct classes of lipid mediators that possess both proinflammatory and proresolving properties. The purpose of this cross-sectional study was to explore the relationship between lipid profiles in human tears and dry eye (DE) symptoms and signs. METHODS: Forty-one patients with normal eyelid and corneal anatomy were prospectively recruited from a Veterans Administration Hospital over 18 months. Symptoms and signs of DE were assessed, and tear samples was analyzed by mass spectrometry-based lipidomics. Statistical analyses comparing the relationship between tear film lipids and DE included Pearson/Spearman correlations and t-tests. RESULTS: Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were present in more than 90% of tear film samples. The ratio of ω-6 (AA) to ω-3 (DHA+EPA) fatty acids was correlated with multiple measures of tear film dysfunction (tear breakup time, Schirmer 2 scores, and corneal staining; all P < 0.05). Arachidonic acid-derived prostaglandin E2 was detected in the majority of samples and correlated with low tear osmolarity, meibomian gland plugging, and corneal staining. CONCLUSIONS: Both ω-3 and ω-6 lipid circuits are activated in the human tear film. The ratio of ω-6:ω-3 tear lipids is elevated in DE patients in proportion to the degree of tear film dysfunction and corneal staining. Metabolic deficiency of ω-3 tear film lipids may be a driver of chronic ocular surface inflammation in DE.

Topical 5-Fluorouracil 1% as Primary Treatment for Ocular Surface Squamous Neoplasia.

PURPOSE: To determine the efficacy of topical 5-fluorouracil 1% (5-FU) as a primary treatment of ocular surface squamous neoplasia (OSSN). DESIGN: Retrospective study. PARTICIPANTS: Topical 5-FU was used as primary therapy in 44 patients with OSSN. METHODS: 5-Fluorouracil 1% administered topically 4 times daily for 1 week followed by a drug holiday of 3 weeks. Patients were identified through a pharmacy database. Patients were excluded if 5-FU was used as adjuvant therapy, if they did not complete therapy, or if they were still actively receiving treatment for OSSN at the time of last follow-up. MAIN OUTCOME MEASURES: The primary outcome measures were the frequency of complete resolution with topical 5-FU treatment and the rate of OSSN recurrence. RESULTS: Of the 44 patients identified, 32 were men and 12 were women. The mean age was 68 years. Complete resolution of OSSN was noted in 82% of patients (36/44); 18% (8/44) were considered treatment nonresponders. Patients were treated with a median of 4 cycles (range, 2-9 cycles). Nasal location was the only risk factor identified for nonresponse to therapy (P = 0.04). The median follow-up after resolution was 10 months (range, 2-77 months). In the 36 patients who showed complete resolution, 4 experienced tumor recurrence. Recurrence rates at 1 and 2 years were 6% and 15%, respectively, using Kaplan-Meier survival analysis. At least 1 side effect from the medication was reported by 61% of patients (21/44), but only 1 patient discontinued the medication because of intolerance. The most common side effect was pain (n = 17; 39%), followed by tearing (n = 10; 23%), photophobia (n = 6; 14%), itching (n = 4; 9%), swelling (n = 2; 5%), and infection (n = 1; 2%). No long-term complications were reported. CONCLUSIONS: 5-Fluorouracil is effective and well tolerated as a primary treatment for OSSN, with 82% of tumors responding completely to therapy.

Effect of a Mediterranean dietary pattern and vitamin D levels on Dry Eye syndrome.

PURPOSE: The aim of this study was to evaluate the association between a Mediterranean dietary pattern (MeDi) and Vitamin D levels on dry eye syndrome (DES). METHODS: This was a cross-sectional study. Male patients seen in the Miami Veterans Affairs eye clinic with normal eyelid, corneal, and conjunctival anatomy were recruited to participate in the study. The patients filled out the 2005 Block Food Frequency Questionnaire and the Dry Eye Questionnaire 5 and underwent measurement of tear film parameters. The serum level of 25-hydroxy vitamin D was also measured. The main outcome measures included the association among MeDi, Vitamin D levels, and DES. RESULTS: Two hundred forty-seven men underwent DES testing. The mean patient age was 69 years (range, 55-95). Using latent class analysis to categorize the presence or absence of disease and quantify its severity, we found that adherence to the MeDi was positively associated with the risk of having DES (odd ratio 1.25, 95% confidence interval, 1.06-1.47, P = 0.007) and with increasing disease severity. Vitamin D levels were not significantly associated with the presence or severity of disease. However, higher levels of vitamin D were associated with decreased DES symptoms, with a -1.24 decrease in median Dry Eye Questionnaire 5 score for every 10-U increase in Vitamin D levels (P = 0.01). CONCLUSIONS: Adherence to the MeDi was not associated with a beneficial effect on DES. Higher vitamin D levels had a small but favorable effect on DES symptoms.

Predictors of ocular surface squamous neoplasia recurrence after excisional surgery.

PURPOSE: To identify predictors of ocular surface squamous neoplasm (OSSN) recurrence after operative resection. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred eighty-nine consecutive patients who underwent excisional biopsy for OSSN lesions at the Bascom Palmer Eye Institute from January 1, 2001, to September 20, 2010. METHODS: Review of pathology records and patient charts. MAIN OUTCOME MEASURES: Identification of factors predictive of OSSN recurrence. RESULTS: Of 389 excised OSSN lesions, 44 recurred during follow-up. The 1-year recurrence rate was 10% and the 5-year recurrence rate was 21%, with a mean time to recurrence in those with a recurrence of 2.5 years (standard deviation, 3.4). Using the American Joint Committee on Cancer (AJCC) clinical staging system, T3 and T2 lesions portended a higher risk of recurrence compared with T1 (T2/T1 hazard ratio [HR], 2.05 [P = 0.04]; T3/T1 HR, 2.31 [P = 0.07]). In addition, a location characteristic that increased the risk of tumor recurrence was tarsal involvement (AJCC T3 stage lesion; HR, 4.12; P = 0.007). Nasal location was associated with a decreased risk of tumor recurrence (HR, 0.41; P = 0.008). Pathologic characteristics significantly associated with tumor recurrence were the presence of positive margins (HR, 2.73; P = 0.008) and higher grade lesions (carcinoma in situ and squamous cell carcinoma versus dysplasia; HR, 2.55; P = 0.02). Treatment with adjuvant cryotherapy significantly decreased the risk of tumor recurrence (HR, 0.51; P = 0.03). In those patients with positive margins, the use of postoperative topical interferon therapy lowered the recurrence rate to a level similar to that of patients with negative margins. CONCLUSIONS: Certain patient and tumor factors are associated with a higher risk of OSSN recurrence after operative excision, such as tarsal tumor location and positive surgical margins. Postoperative adjuvant therapy should be considered in patients with high-risk OSSN characteristics.