Update on Diagnosis and Management of Conjunctival Papilloma

Conjunctival papilloma is an acquired benign squamous cell tumor that can present at any age,but most frequently in the third and fourth decades of life.Papillomas have been associated with human papilloma virus(HPV)infection,usually types 6 and 11.Although histopathological diagnosis remains the gold standard,the advent of newer non-invasive imaging modalities such as optical coherence tomography(OCT)is transforming the way we diagnose and treat ocular surface tumors,including conjunctival papilloma.Management of these lesions can prove a challenge to the treating physician since not all lesions respond to medical and/or surgical therapy and in fact may worsen after surgical manipulation.In this review,the epidemiology,pathophysiology,clinical characteristics,and diagnosis of conjunctival papilloma including the use of OCT are discussed.Indications,efficacy,and side effects of currently available management options are also reviewed to guide the selection of the best treatment approach.

Classification, diagnosis, and management of conjunctival lymphoma

Lymphoma is a malignant lymphoproliferative tumor that can involve the conjunctiva.Approximately 5–15%of all extranodal lymphomas are found in the ocular adnexal region,with approximately 25%of those involving the conjunctiva.Ninety-eight percent of conjunctival lymphomas arise from B-lymphocytes.The most common subtype of conjunctival lymphoma is extranodal marginal zone lymphoma(80%),followed by follicular lymphoma(8%),diffuse large B-cell lymphoma(3%)and mantle cell lymphoma(3%).Natural killer and T cells(NK/T)are rare causes of lymphoma.While most conjunctival lymphomas are localized to the ocular adnexa at the time of presentation,systemic examination and management are of key importance in the long-term care of the patient.This review outlines the classification,etiology,presentation,diagnosis,and management of conjunctival lymphoma.The novel use of high resolution optical coherence tomography,both as a diagnostic tool and as a means for ongoing evaluation during treatment,is illustrated.Treatment options discussed include external beam radiation,chemotherapy,immunotherapy,antibiotic therapy,and combination regimens.Future investigation of the etiology and pathogenesis of conjunctival lymphoma is expected to reveal opportunities for innovative and individualized therapeutic agents.Collaboration between multiple disciplines is key in the advancement of the field.

Optical coherence tomography for ocular surface and corneal diseases: a review

The advent of optical coherence tomography(OCT)imaging has changed the way ophthalmologists image the ocular surface and anterior segment of the eye.Its ability to obtain dynamic,high and ultra-high resolution,cross-sectional images of the ocular surface and anterior segment in a noninvasive and rapid manner allows for ease of use.In this review,we focus on the use of anterior segment OCT,which provides an“optical biopsy”or in vivo imaging of various ocular surface and corneal pathologies,allowing the clinician to diagnose diseases otherwise not visualized by traditional methods.The utility of anterior segment OCT for various anterior segment pathologies is reviewed.

The use of high resolution anterior segment optical coherence tomography for the characterization of conjunctival lymphoma, conjunctival amyloidosis and benign reactive lymphoid hyperplasia

Background:Conjunctival lymphoma,conjunctival amyloidosis and benign reactive lymphoid hyperplasia(BRLH)are conditions that often have a similar appearance on the ocular surface.The use of high resolution anterior segment optical coherence tomography(HR-OCT)enables clinicians to evaluate distinctive differences in tissue morphology and cellular patterns in various ocular surface conditions.In this study,we characterize the morphological differences seen in conjunctival lymphoma,conjunctival amyloidosis and BRLH on HR-OCT imaging.Methods:A retrospective chart review was performed of patients with biopsy proven conjunctival lymphoma,conjunctival amyloidosis and BRLH between 2012 and 2019 at the Bascom Palmer Eye Institute.Patients were excluded if HR-OCT imaging was not performed on initial presentation.Results:Thirty-four total eyes of 27 patients were identified.Twenty eyes had conjunctival lymphoma(16 patients),8 eyes had conjunctival amyloidosis(6 patients)and 6 eyes had BRLH(5 patients).All conditions appeared clinically as pink,red or yellow subepithelial lesions but had different features on HR-OCT.In lymphoma,HR-OCT images typically showed homogenous,dark subepithelial lesions with smooth borders,containing monomorphic dot-like infiltrates.HR-OCT images of amyloidosis typically showed heterogeneous,dark lesions with irregular borders,often containing hyperreflective linear infiltrates.HR-OCT images of BRLH showed variable infiltration of the subepithelial tissue,at times with homogenous lesions containing dot-like infiltrates like lymphoma and other times with more hyperreflective,subepithelial tissue.Flow cytometry and gene rearrangement was needed for final differentiation between BRLH and lymphoma lesions.Conclusions:Distinctive features on HR-OCT of conjunctival lymphoma,conjunctival amyloidosis and BRLH can help characterize these lesions beyond what is apparent with the clinical examination.Future studies can further validate this technology’s use with more subtle and challenging lesions.

Update on pharmacotherapy for ocular surface squamous neoplasia

The most frequently encountered non-pigmented tumor of the ocular surface is ocular surface squamous neoplasia(OSSN).Over the past two decades,the pharmacological management of OSSN has grown,with topical 5-fluorouracil,mitomycin,and interferon alpha 2b all being successfully used to treat this disease.Other agents,such as anti-vascular endothelial growth factor(VEGF),retinoic acid,cidofovir and Aloe vera,have less frequently been used in the treatment of OSSN.This review will discuss these pharmacologic agents,summarizing available data and presenting the approach to the treatment of these tumors.

Epidemiology of ocular surface squamous neoplasia in veterans: a retrospective casecontrol study

Background:A number of risk factors have been evaluated in ocular surface squamous neoplasia,but few studies have assessed risk factors specific to the armed forces veteran population.Methods:We conducted a retrospective case-control study on 55 patients and 55 age-matched controls with biopsy-proven ocular surface squamous neoplasia from the Miami Veterans Administration Hospital Eye Clinic to investigate potential risk factors encountered by veterans,including service-specific exposures.Veteran-specific risk factors included ionizing radiation exposure,Agent Orange exposure,deployment to Southwest Asia,and exposure to the series of biochemical warfare tests known as Project Shipboard Hazard and Defense.Data was analyzed with SPSS(SPSS Inc.,Chicago,IL)using t-tests,chi-squared,and logistic regression analysis,with a p-value of<0.05 considered statistically significant.Results:The strongest risk factor for ocular surface squamous neoplasia was lifetime sun exposure both directly assessed via historical quantification of exposure by dermatology practitioners(Odds Ratio(OR)5.4,95%Confidence Interval(CI)2.27–12.847,p<0.005),and using the surrogate markers of basal cell carcinoma(OR 3.157,95%CI 1.286–7.748,p=0.010)and pingueculae(OR 5.267,95%CI 2.104–13.186,p<0.005).Of the veteran-specific risk factors,Agent Orange exposure and Southwest Asia deployment were not associated with an increased risk of ocular surface squamous neoplasia.Exposure to ionizing radiation and involvement in Project Shipboard Hazard and Defense were not documented among any cases or controls.Conclusions:The results of our study are consistent with prior established risk factors,namely highlighting the important role of sun exposure in ocular surface squamous neoplasia among veterans.

Utility of high-resolution anterior segment optical coherence tomography in the diagnosis and management of sub-clinical ocular surface squamous neoplasia

Background:To evaluate the frequency and characteristics of sub-clinical ocular surface squamous neoplasia(OSSN)detected by high-resolution anterior segment tomography(HR-OCT)in patients with clinically unapparent disease following topical treatment.Methods:A retrospective chart review of patients with OSSN identified through a pharmacy database at the Bascom Palmer Eye Institute from January 2013 to December 2018 was conducted.Patients undergoing primary therapy with topical 5-fluorouracil 1%(5-FU)(4 times a day for 7 days with a 21-day break)or interferon-alpha-2b(IFN)(4 times a day)were reviewed.Patients were separated into two groups.Group 1 included individuals whose clinical resolution of OSSN aligned with complete resolution on HR-OCT.Group 2(sub-clinical OSSN group)included individuals with clinical OSSN resolution but with features of persistent disease on HR-OCT.Patients excluded included those treated at an outside institution and those who used topical therapy as a surgical adjunct.Results:A total of 95 patients(95 eyes)were reviewed.Sub-clinical OSSN was detected at a frequency of 17%in our study patients(n=16 patients,9 treated with 5-FU and 7 treated with IFN).In the 16 individuals,the mean time to clinical resolution was 3.6±1.0 cycles for 5-FU and 4.0±0.0 months for IFN.An additional 2.1±0.8 cycles for 5-FU and 1.2±0.4 months for IFN were needed to achieve HR-OCT resolution of OSSN.Recurrence in Group 1 was noted in 10 patients(12%)while no recurrences occurred in Group 2,the cohort with subclinical disease that received the extended medical therapy.The mean follow-up was 24.0±17.9 months.Conclusion:We found that at least 17%of individuals with apparent clinical resolution of OSSN have sub-clinical disease detected on HR-OCT.This information can be used to optimize treatment and extend therapy past the point of clinical resolution.