Juan Carlos Murillo

Recruitment of Donor T Cells to the Eyes During Ocular GVHD in Recipients of MHC-Matched Allogeneic Hematopoietic Stem Cell Transplants

PURPOSE The primary objective of the present study was to identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage. METHODS Graft-versus-host disease was induced using an major histocompatibility complex (MHC)-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant (HSCT) model. This approach, which utilized congenic and EGFP-labeled donor populations, mimics a matched, clinically unrelated donor (MUD) cell transplant. Systemic and ocular GVHD were assessed at varying time points using clinical examination, intravital microscopy, immune phenotype via flow cytometric analyses, and immunohistochemical staining. RESULTS Following transplant, we observed characteristic changes in GVHD-associated immune phenotype as well as clinical signs present in recipients post transplant. Notably, the kinetics of the systemic changes and the ocular damage paralleled what is observed clinically, including damage to the cornea as well as the conjunctiva and lacrimal gland. Importantly, the infiltrate contained predominantly donor CD4 as well as CD8 T cells with an activated phenotype and macrophages together with effector cytokines consistent with the presence of a TH1 alloreactive population. CONCLUSIONS Overall, the findings here unequivocally demonstrated that donor T cells compose part of the corneal and ocular adnexa infiltrate in animals undergoing ocular GVHD. In total, the results describe a novel and promising preclinical model characterized by both systemic and ocular changes as detected in significant numbers of patients undergoing GVHD following allo-HSCT, which can help facilitate dissecting the underlying immune mechanisms leading to damage associated with ocular GVHD.

Intracorneal and Intraocular Invasion of Ocular Surface Squamous Neoplasia after Intraocular Surgery: Report of Two Cases and Review of the Literature

Purpose: The aim of this paper was to describe 2 cases of ocular surface squamous neoplasia (OSSN) of the conjunctiva with intracorneal and intraocular extension following intraocular surgery. Methods: We conducted a clinical pathological retrospective case series. Results: Case 1 underwent cataract surgery in the setting of an unnoticed adjacent OSSN. An excisional biopsy with cryotherapy and intraoperative mitomycin C was subsequently performed, confirming OSSN. The patient had two recurrences treated topically with resolution. While the conjunctiva remained clear, a corneal haze emanating from the cataract incision site was noted. Penetrating keratoplasty (PK) for this haze revealed midstromal infiltrative carcinoma. Case 2 had a history of herpes simplex keratitis that ultimately required corneal grafts. Fifteen years later, he developed an OSSN treated with excisional biopsy and had clear margins. Eight months later, he presented with a recurrence of his OSSN and was treated briefly with topical interferon for 4 weeks; however, he developed an infectious keratitis with a corneal perforation requiring another PK. Four months after PK, low-grade inflammation was noted. Cytology of the anterior chamber aspirate revealed neoplastic squamous cells. Another PK was then performed. Pathology confirmed extensive intraocular neoplasia. Limited exenteration was performed. Conclusion: Patients with a history of OSSN may be at increased risk of neoplastic intraocular extension following intraocular surgery.

Surgical versus medical treatment for ocular surface squamous neoplasia: A quality of life comparison

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.

Ocular Surface Parameters Predicting Patient Satisfaction After a Single Vectored Thermal Pulsation Procedure for Management of Symptomatic Meibomian Gland Dysfunction

Purpose: To evaluate the ocular surface parameters that could predict patient satisfaction after single application of vectored thermal pulsation (VTP). Methods: This is a retrospective interventional case series; it included consecutive patients who underwent bilateral VTP for management of symptomatic meibomian gland dysfunction (MGD). Patients received a full ocular surface evaluation. The outcome was patient subjective improvement during the first 3–4 months after 3 follow-up visits. For analysis, patients were divided into responders and nonresponders. Results: Forty-nine patients received bilateral treatment, with 32 patients (65.3%) reporting subjective improvement after treatment. Responders had lower tear production (6.9 ± 5.9 mm vs. 13.6 ± 6.8 mm; t test P = 0.002), a higher corneal staining score (4.4 ± 5.0 vs. 0.43 ± 1.1; t test P = 0.003), and a higher conjunctival staining score (3.1 ± 2.4 vs. 1.5 ± 1.8; t test P = 0.023) and presented with a higher tear osmolarity (319.7 ± 23.22 mOsm/L vs. 306.9 ± 9.0 mOsm/L; t test P = 0.029) than the nonresponder group. We found no association between patient age, tear breakup time, Ocular Surface Disease Index score, tear lipid layer thickness, or MGD grading score, as measured before intervention, with patient-perceived success of treatment. No complications to treatment were noted, and no patient reported worsening of preexisting symptoms on follow-up. Conclusions: VTP can be effective in treating dry eye symptoms of patients with MGD. Our data show that objective findings of dry eye, as evidenced by lower tear production, higher corneal and conjunctival staining scores, and higher osmolarity, tend to be markers present in the group of patients responding positively to VTP.