Pathology of the eye encompasses a wide variety of conditions that impact vision. Our lab processes clinical specimens provided by surgeons from Cornea and Oculoplastic divisions as well as those collected as part of experimental research studies.

Maintain a comprehensive history of symptoms. Patients experiencing persistent eye pain should be evaluated for potential systemic diseases that could be the source.

Retinal Dysplasia

Retinal dysplasia, which refers to abnormal development of the retina, can affect either one or both eyes and can vary in severity; focal, multifocal, and geographic forms exist. Focal retinal dysplasia presents as streaks and dots in the central area of each eye while multifocal dysplasia displays irregular or horseshoe-shaped areas with increased or decreased reflectivity; geographic retinal dysplasia is more severe as dogs with this condition are blind; hereditary factors often play a part. Retinal dysplasia runs rampant among many breeds.

Dogs born with this condition usually inherit it; however, it can also arise as a result of in utero infection with feline leukemia virus or feline panleukopenia infection, radiation exposure during gestation, vitamin A deficiency or genetic defects. A CERF examination can detect it early as 6-8 weeks in puppies – although young puppies often wiggle out during examinations due to an unwillingness to remain still during an exam session. Severe forms can result in retinal detachment leading to blindness while milder forms appear as rosette-like formations in dogs’ retinas while nonprogressive nonheritable changes are also commonly observed among cats and other species.

Medulloepithelioma

A 34 year old male presents with redness and pain over six months due to trauma from a metallic foreign body placed 6 months prior.

He is being treated at Wills Eye Ocular Oncology Service. The family was informed that medulloepithelioma is an uncommon ciliary body neoplasm typically diagnosed in children before the age of 10. Tumors can either be classified as nonteratoid or teratoid depending on whether only medullary epithelial cells are involved or also contain characteristics from bone, cartilage and skeletal muscle; both types have high rates of local recurrence with potential high rates of localized recurrences with high localized recurrence rates of local recurrences with high rates of localized recurrences as well as high rates of iris neovascularizations.

Histopathologic examination reveals poorly differentiated cells with ribbon-like structures exhibiting polarity and filled with mucinous material that forms cysts in the ciliary body. The highly vascularized tumors contain dense collagenous connective tissue surrounding them that prevents proper drainage of fluid from the eye, creating high intraocular pressure levels. Recurrence rates following local resection can be high, necessitating in many instances complete enucleation for cure.

Any child exhibiting unexplained iris neovascularization should be presumed to have medulloepithelioma until proven otherwise. When diagnosed, any recurrent medulloepitheliomas should be evaluated by Wills Eye Ocular Oncology Services in order to develop the optimal treatment strategy; five of ten patients treated locally while six required enucleation. Plaque radiotherapy has proven highly successful over time as an alternative approach.

Retinal Angiomatosis

Retinal angiomatosis is a rare retinal tumor associated with von Hippel-Lindau disease that forms capillary hemangioblastomas in either the retina or optic nerve, typically without symptoms; they develop from capillaries within retinal pigment epithelium capillaries and often exude fluid and exudates. Sometimes they even lead to vitreous hemorrhage or retinal detachment.

As for treatments of retinal angiomatosis, photodynamic therapy and laser photocoagulation have both been utilized, although evidence for their efficacy remains limited. Recently, however, an intravitreal combination of triamcinolone acetonide and photodynamic therapy was demonstrated as being effective at managing RAP found among those diagnosed with Neovascular Age-Related Macular Degeneration.

Von Hippel-Lindau disease typically manifests initially through retinal pigment epithelium changes or retinal pigment epithelium traction; approximately 70% of VHL gene carriers by age 25 years will experience at least one RAP lesion as their first sign. Although often asymptomatic, RAP lesions may lead to vision-threatening complications, including vitreous hemorrhage or exudates that lead to macular involvement, retinal pigment epithelium traction or pseudopapilledema.

Fd-OCT provided unprecedented in vivo detail of retinal angiomatosis lesions in this retrospective case series of five patients clinically diagnosed with retinal angiomatosis, providing unprecedented in vivo details that closely resemble histologic specimens. All five lesions were located deep retina and showed areas of neovascularization around hemangioblastomas; three out of the four cases also displayed well-defined boundaries with the Bruch membrane.

Retrospective observational case series was performed to evaluate the visual outcomes of Chinese patients treated for retinal angioma- tout proliferation with photodynamic therapy or laser photocoagulation at a tertiary eye hospital. Patients were identified through physical exam, fluorescein and indocyanine green angiography and medical records; Kaplan-Meier analysis revealed that eyes with large angioma- tout proliferations and symptoms at initial diagnosis had significantly poorer visual outcomes compared with eyes without symptoms at initial diagnosis.

Retinal Lymphoma

This case centers on a 75-year-old female patient who presented with bilateral floaters and poor vision, leading to an enucleation and subsequent histopathology analysis that demonstrated pseudohypopyon with necrosis areas containing large B cells that appeared both vitreously and retinally; these appeared similar to neoplastic large B cell manifestations found in primary vitreoretinal lymphoma (PVRL), or diffuse large B-cell lymphoma of the central nervous system (DLBCNS).

PVRL is considered a high-grade malignancy due to its extensive CNS involvement. Neoplastic B-cells with PVRL possess a characteristic morphology and express various chemokines and receptors as well as interleukins such as IL-10; immunophenotyping, flow cytometry and cytokine analysis help diagnosis while somatic mutations in immunoglobulin genes may provide additional assistance.

PVRL patients usually exhibit diffuse vascular leakage on fluorescein angiography (FA), punctate hyperfluorescent window defects in the sub-RPE area and round, hypofluorescent lesions known as the leopard spot pattern. Spectral-domain optical coherence tomography and fundus autofluorescence are extremely helpful tools in characterizing VRL by showing its characteristic vascular leakage, cell infiltration and leopard-spot pattern.

Even with its high recurrence rate, systemic chemotherapy treatments such as methotrexate, temozolomide, rituximab induction; etoposide consolidation; and lenalidomide maintenance appear effective against tumor growth in this disease. If persistent dense vitreous infiltrates persist therapeutic vitrectomy may be required.

Arun Dev Singh is currently Professor of Ophthalmic Oncology at the Cole Eye Institute, Cleveland Clinic Lerner College of Medicine in Cleveland, Ohio. Educated at University of Madras and All India Institute of Medical Sciences New Delhi before going on to complete both MD and FRCS (Edin) credentials in Edinburgh Scotland. As a Fellow of the Royal College of Ophthalmologists in the UK, he currently directs the Department of Ophthalmic Oncology within Cole Eye Institute at Cleveland Clinic Foundation. Dr. Hoegerl has published several papers in ophthalmic oncology and is editor-in-chief of the British Journal of Ophthalmology, while receiving an American Academy of Ophthalmology Senior Achievement Award. His clinical interests encompass ophthalmic oncology, ocular trauma management and treating recurrent viral ocular infections; additionally he serves as reviewer for several journals as well as being invited speaker at national and international conferences.