The presence of specific ocular lesions was associated with a higher frequency of bone marrow relapses and CNS involvement, leading to a lower survival rate[11]. Leukemic retinopathy is the term most often used to denote the fundus manifestations of anaemia, thrombocytopenia and hyperviscosity observed in patients with leukaemia[12]. Experts believe that leukemic retinopathy is associated with abnormal hematologic parameters and coagulopathy[13, 14]. Our patient presented with bilateral retinal vein dilatation and tortuosity, blot and flame-shaped retinal hemorrhages, and serous retinal detachment, features that were the result of both direct retinal leukemic infiltration and leukostasis secondary to hyperleukocytosis[15]. However, serous retinal detachment (SRD) in her LE has been reported less commonly in the setting of acute leukemia and may develop as a result of choroidal involvement by leukemic cells causing retinal pigment epithelial disturbances or due to incompetence of the outer blood‒retinal barrier (BRB), which induces retinal pigment epithelial changes[16, 17]. Although they are more common in acute (vs. chronic) leukemia, they are less common in patients with the lymphoid (vs. myeloid) subtypes, females and older patients, making our patient an unlikely suspect [18]. Hyperreflective specks in the vitreous give the impression of vitreous seeding and considered as leukemic infiltrates. This may be caused by the leukaemic cells entering the vitreous from optic disk neovascularization, and vitreous haemorrhage allows neoplastic cells to enter the vitreous cavity, similar to the presentation in our case[19].
With the increase in survival of patients with leukemia, the incidence of CNS relapse is on the rise. The optic nerve can reveal leukemic involvement of the CNS[20]. However, optic nerve infiltration as an initial sign of relapse is quite rare. The eyes and optic nerves are identified as pharmacological sanctuaries for leukemia therapy because the BRB shields the CNS from any systemically administered chemotherapeutic drugs[21]. Thus, many adjuvant therapies are often required to achieve complete remission. In our patient, bone marrow and CSF aspiration showed massive leukemic cells, while the CSF open pressure was normal. Researchers have postulated that one does not have to suspect increased intracranial pressure to explain swelling of the optic nerve since leukemic infiltration through the central retinal vessels and vessels in the pial septa is sufficient to cause venous congestion and/or ischemia with edema[22]. Optic neuropathy in the context of leukemia can be diagnosed through a broad variety of methods, including infiltration, infections, compression, vasculitis, radiotherapy-induced complications or adverse effects of chemotherapeutic agents[23–25]. All these possibilities should be excluded through careful investigations. There were no signs of infection. Furthermore, the absence of neurologic and dermatologic signs, such as dysacusis, vitiligo, and poliosis, is not consistent with Harada's syndrome. A diagnosis of leukemic optic nerve infiltration was highly considered. An 8-week follow-up appointment at the ophthalmology clinic demonstrated functional and anatomic improvement in both eyes. In the present case, cerebral MRI showed no enhancement of the optic nerve top or bottom, which also explains that radiological features are neither specific nor sensitive for ocular leukemia[26]. A recent review illustrated the poor sensitivity of CSF cytology[27]. Of note, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting disease relapse. Progress in the research and therapy of adult ALL is accelerating[28], and future studies should investigate better approaches for the early diagnosis of relapsed disease and more intensive strategies to improve patient survival.
In summary, understanding ocular involvement in leukemia is crucial since the eye is the only organ where leukemic infiltration to nerves and blood vessels can be observed directly. Recognizing fundus changes in leukemia allows earlier diagnosis and prompt treatment. Ophthalmologists should be aware of these possible manifestations and possible etiologies in patients with ALL, even if they have achieved disease remission. In this report, we present an unusual case of bilateral optic nerve infiltration and leukemic retinopathy as initial signs of Ph+-ALL relapse with CNS involvement in an elderly female and explore the underlying proposed pathologic basis of these ocular manifestations in leukemia. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting disease relapse.