Diagnosis of intraocular lymphoma requires a high degree of clinical suspicion [1]. Due to different treatment approach and effect on survival, differentiating this entity from ocular inflammation is of utmost importance. In our case, ten months prior to the diagnosis of PVRL, there were two OCT signs that, in a retrospective evaluation, were suggestive for the disease when it was still subclinical. The first sign was two hyper-reflective lines with vertical orientation from outer nuclear layer and EZ in the foveola. These vertical lines may be a precursor to sub-RPE infiltrations, and some may be a relation between retinal vessels involvement and sub-RPE deposits, according to some theories [5] Deak et al. hypothesized that these vertical lines may represent early microinfiltrates originating from retinal capillaries, which cannot be recognized in fundus examination. They observed these lines in more than half of their cases. It is worth noting that, sometimes orientation of these lines in relation to OCT B-scans may be oblique, and these lines may appear in inner retina while the rest of B-scans illustrate the line in outer retina. The second OCT sign in our case was drusenoid lesions in macular area, which may be interpreted as aging process or early stages of dry type age-related macular degeneration. Other OCT features have been reported in the literature for PVRL including infiltrations in the inner layers of the retina, discrete nodules of hyperreflective foci in the subretinal space, and confluent bands of hyperreflective foci in the subretinal or sub-RPE space [5, 6]. Based on a case series by Barry et al., each of these OCT features was observed in less than one third of cases [6]. The gold standard test for diagnosis of PVRL is histopathologic investigation of or chorioretinal specimen [7].
The origin of atypical B lymphocytes inside the eye is still questioned in this disease [8]. In addition to typical features of vitreous and subretinal and sub-RPE infiltration, other rare ocular presentations reported for PVRL are vitreous hemorrhages, retinal vasculitis, optic nerve infiltration, and rarely serous retinal detachment [9]. Despite having had RRD surgically repaired, our patient’s PVRL appearance was typical. Therefore, it seems that although previous retinal surgery may not alter the typical signs of PVRL, it may alter the treatment response. Malignant lymphocytes infiltrated the vitreous cavity and anterior segment in our case. It has been postulated that in some patients with empty vitreous, such as vitrectomized eyes, anterior segment manifestations such as corneal edema and KPs may occur more frequently [10].
Treatment is controversial when there is isolated ocular involvement. Local treatment with intravitreal methotrexate (MTX) (400 μg/0.1 cc) is the preferred strategy [1]. It is known that the half-life of the injected drug in the vitreous may be much shorter in a vitrectomized eye. Lee et al. demonstrated the enhanced clearance (more than 10 times) of vascular endothelial growth factors (VEGFs) in vitrectomized eyes [11]. Also, it was stated that aberrant multidrug resistance-related protein (MRP), reduced folate carrier (RFC), and folate binding protein (FBP) expression in the human leukemia cells’ membrane, which might have occurred after multiple intravitreal MTX injections, could disrupt the maintenance of cellular folate homeostasis. They also change the transport of drug across the cells that contribute to resistance following repeated intravitreal injections [12, 13].
As the drug has better access to the vitreous compared to the subretinal space, it could justify the differences therapeutic responses between vitreous malignant cells compared to subretinal infiltrations in our patient. These may explain the reasons why our patient did not respond adequately to the applied treatment.
In these cases, alternative approaches such as ocular irradiation or more frequent injections or higher doses of MTX as well as applying other cytotoxic agent such as rituximab, thiotepa,melphalan or autologous peripheral blood stem cell transplantation may be helpful [14,15,16,17]. To validate these approaches, further studies are needed.
This is the first article to explain how PVRL manifests itself shortly after retinal detachment surgery and how it responds to treatment. OCT has an indispensable role in the diagnosis and treatment response which was proved by pathology.
