Oxaliplatin is a platinum-based drug and is prescribed in combination with fluorouracil and leucovorin in a famous combination known as Folfox which is one of standard treatments for advanced colorectal cancer. [8,9] Ocular side effects of Oxaliplatin are rare and clinicians usually notice to other possible side effects of this drug like neurotoxicity or hematologic adverse effects. Oxaliplatin has been reported to induce different ocular impairments, most of them are reversible and in some cases, it has been permanent [1,6].

In a case report by Mesquidaa et al. for the first time a patient with permanent damage to RPE following Oxaliplatin administration is reported. There has been no alteration in the retina in funduscopy but in visual field examination bilateral concentric scotoma was reported with diminished EOG response in both eyes and OCT as well as ERG had normal results [10]. Our patient also showed permanent damage, and it thus differs from previously described Oxaliplatin induced ocular toxicities, which are usually transient and reversible. It may be related to delay in diagnosis. The changes in OCT were stable without any recovery in our patient, although her ERG response showed some improvement. It might be related to some degrees of recovery that is revealed as functional improvement without any significant structural changes. On the other hands, the recovery in structure maybe needs more time. Early intervention and cessation of the drug would improve the condition and cause reversible changes.

Our case is the second report of RPE damage following Oxaliplatin administration but with new findings (crystalline retinopathy). It is the first case showing iridescent white dots spread through funds in both eyes and also outer retina and RPE atrophy in OCT of both eyes.

In Oxaliplatin pharmacolo-chemistry there is oxalic acid components and chlorine ligands are replaced by the oxalato bidentate derived from oxalic acid for water solubility improvement and it may explain the yellow dot pattern and in fact possible crystalline retinopathy which was visible in our patient.[9] Crystalline retinopathy was reported in several conditions like chronic retinal detachment, primary hyperoxaluria, Bietti crystallin dystrophy,  talc emboli, and cystinosi or following specific chemical medications like canthaxanthin, methoxyflurane, tamoxifen, nitrofurantoin and etc [11]. Due to component of Oxalipaltin, occurrence of crystalline retinopathy can be possible in administration of this drug, although it has not been reported previously.  This is the first report of crystalline retinopathy due to Oxaliplatin usage. In crystallin retinopathy associated with methoxyflurane toxicity dose related deposition of oxalate crystals occurs in retina. In examination yellow crystals are visible often in an arterial distribution throughout the retina, at the level of the RPE [12]. Our patient had scattered yellowish iridescent dots in posterior pole of both eyes and also anterior to arcades which were more visible around arteries (Figure 1).

In primary hyperoxaluria an autosomal recessive disease with overproduction of oxalate in body, fundus autofluorescence scattered hyper auto fluorescent dots corresponding to crystals will be observed and in SD-OCT images hyper reflective spots in regions of RPE elevation will be found in addition to atrophic changes of macula.[12] In our case SD-OCT images showed outer retina and RPE atrophy mainly in macula with scattered hyper-autoflurescent spots not only through outer retina and RPE but also choroid as its mentioned in some oxalate retinopathy conditions like primary hyperoxaluria [12].

It is difficult to establish an association between a specific drug and visual disturbances because of the low incidence of these side effects and also existence of multiple simultaneous factors which can cause ocular sign and symptoms.

One of the most important differential diagnosis of our case was cancer associated retinopathy or CAR. Like toxic retinopathy associated with Oxaliplatin there is no single diagnostic criterion for CAR. The clinical symptoms in CAR have a usually acute or sub-acute presentation. It is usually diagnosed according to clinical suspicion of normal funds at the early periods of the disease in spite of severe ERG response attenuations, positive anti-retinal antibodies in lab date, and atrophic changes in RPE [13].

Symptoms in our case were not so acute and progressive and also it regressed following oxaliplatin cessation, we didn’t test antirational antibody for the patient because of economic burden of this test for the patient and that more than 40% of the patients with CAR will have negative autoantibodies against retinal antigens. Also, positive tests for these autoantibodies are reported in healthy individuals [14]. Significant improved ERG response after 3 months after discontinuation of Oxaliplatin usage strengthened the diagnosis of drug toxicity other than CAR. On the other hand, improvement of ERG response without any intervention was not compatible with the diagnosis of CAR. Decreased ERG response could be associated with minimal changes in fundus on the contrary our case. Reduction in Arden ratio usually is mild in CAR in contrast our patient.[14] Overall, these findings coincided with the diagnosis of drug toxicity other than CAR.