Cytopathology of Vitreous Specimens in Acute Retinal Necrosis

ABSTRACT

Purpose

To report the cytopathology of vitreous biopsy samples in patients with acute retinal necrosis (ARN) who underwent pars plana vitrectomy (PPV). We also describe two patients with unique clinical courses, cytopathologic findings, and immune response

Methods

A retrospective review of patients with ARN who developed retinal detachment (RD) and underwent PPV from 22011 to 2019 at the Emory Eye Center was performed to assess cytopathology findings of vitreous biopsy samples. Patient demographics and laboratory testing including aqueous humor PCR for viral pathogens were recorded. Additional clinical details abstracted included intravitreal injections, surgical procedures, and vitreous cytopathological reports including immunohistochemistry findings.

Results

Fourteen eyes of 12 patients with RD were reviewed. Ten eyes showed HSV DNA (71%) and 4 demonstrated VZV DNA (29%). All eyes received intravitreal antivirals (i.e. ganciclovir or foscarnet) with a median of 8.5 intravitreal injections per eye. Diagnoses prompting PPV included tractional RD in 14 eyes (100%), rhegmatogenous RD in 8 eyes (57%), vitreous hemorrhage in 4 eyes (29%) and vitreous opacity in 4 (29%). Ophthalmic pathology reports showed lymphocyte populations in 10 eyes (71%) with a CD3 + T-cell predominance in two patients where immunohistochemistry of CD3+ and CD20+ for T- and B-cell populations was performed. Observed immune cell populations included macrophages or histiocytes (11 eyes, 79%) and polymorphonuclear cells in 4 eyes (29%). Initial median VA was 2.5 (IQR 2.0–3.0) and improved to 2.0 (IQR 1.48–3.00, p = .48) at 6-months and 1.8 (IQR 1.2–3.0, p = .45) at 12 months follow-up.

Conclusions

Our cohort of ARN patients undergoing PPV show a spectrum of immunologic findings with the majority demonstrating a lymphocytic response. Histiocytes, macrophages, and PMNs were also observed. Cytopathologic and immunologic studies suggest that both innate and adaptive immunity are responsible for the clinical disease findings observed in ARN. The variability of the response to treatment in patients with ARN may reflect patient-to-patient differences in their antigen-specific immune response. Understanding the immunologic response associated with ARN may provide valuable information regarding the dosing and timing of treatment.

KEYWORDS:

• acute retinal necrosis
• panuveitis
• cytopathology
• foscarnet
• clonal rearrangement

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Prior presentation

This data was presented in part at the American Uveitis Society meeting at the American Academy of Ophthalmology Annual Meeting in San Francisco, CA, October 2019.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This project was supported by the National Eye Institute/National Institutes of Health core grant [P30-EY06360] (Department of Ophthalmology, Emory University School of Medicine), National Eye Institute of the National Institutes of Health under award number [K23 EY030158] (Shantha) and [R01 EY029594] (Yeh). This research was also supported an unrestricted departmental grant from Research to Prevent Blindness, Inc. to the Emory Eye Center, Emory University School of Medicine, the Bayer Global Ophthalmology Awards Program, Association for Research in Vision and Ophthalmology Mallinckrodt Young Investigator Award (SY), and National Institutes of Health funding for the Emory Center for AIDS Research (Kraft, P30AI050409). This research is also supported by the Stanley M. Truhlsen Family Foundation, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.