Study design
Retrospective case series.
Ethics approval
The research adhered to the tenets set forth in the Declaration of Helsinki and was approved by our local ethics committee (CE 2023/157). Written informed consent for publication was obtained from both patients.
Case descriptions
Case 1
An 18-year-old man complained of visual field defects, mostly at nighttime, that started during childhood. There was no notable general or family history. He was of Moroccan ethnicity, and was not taking any medication.
On examination, best-corrected visual acuity (BCVA) was 20/32 in both eyes (OU). Slit-lamp examination (SLE) was normal except for 1+ anterior vitreous cells (AVC). Fundoscopy showed vascular attenuation and mid-peripheral outer retinal atrophy (ORA) (Fig. 1, A – B). There were no intraretinal pigment migrations (IPMs). Macular spectral-domain optical coherence tomography (SD-OCT) showed CME and perifoveal ORA (Fig. 1, C – D). Fluorescein angiography (FA) demonstrated peripapillary leakage and CME (Fig. 1, E – F). Humphrey 24-2 visual fields (HVF) showed pericentral sensitivity loss. Full-field electroretinogram (ffERG) was uninterpretable because of contact lens electrode aversion.
Posterior uveitis (PU) in the form of peripapillary retinal capillaritis was suspected and a targeted uveitis work-up (syphilis, tuberculosis, sarcoidosis, Birdshot retinochoroiditis [BRC]) was negative. Owing to perifoveal ORA, RP masquerading as PU was then suspected and an inherited retinal disease (IRD) gene panel was ordered.
Treatment for waxing and waning CME was initiated with partial and inconsistent response. This included oral methylprednisolone, oral methotrexate (MTX), anti-VEGF intravitreal injections (IVT), MTX IVT, dexamethasone implant (DEX) IVT, and intravenous (IV) infliximab, before obtaining CME and RVL control using IV TCZ 8mg/kg every 4 weeks (Fig. 1, G – J).
Ultimately, a homozygous pathogenic variant in the EYS gene was found and a diagnosis of EYS-related autosomal recessive RP was made. Scarce peripheral IPMs had appeared over the follow-up.
Comprehensive explanations were given to the patient concerning the genetic nature of the disease, and the absence of a specific treatment. However, considering the obvious benefit of TCZ on the inflammatory component of the disease, the patient opted to pursue treatment.
At the last follow-up, macular SD-OCT remained dry under IV TCZ 8mg/kg every 8 weeks. Final BCVA was 20/25 OU.
Case 2
A 61-year-old woman presented with nyctalopia, difficulty stumbling over things, and photopsia for the past year. She was of Chinese ethnicity, and had a history of cysticercosis for which she had been inconsistently self-medicating with praziquantel.
On examination, BCVA was 20/30 in the right eye, and 20/25 in the left. SLE was normal. Fundus examination revealed subtle mid-peripheral ORA, and mild vascular attenuation (Fig. 1, M – N). Macular SD-OCT showed symmetrical perifoveal ORA, and CME (Fig. 1, O – P). FA revealed intense vascular leakage from the optic disc, veins, capillaries, and fovea (Fig. 1, Q – R). HVF showed concentric defects. ffERG revealed rod-cone dysfunction (RCD). Overall, findings were felt to be compatible with RP and an IRD gene panel was ordered.
However, owing to intense CME and RVL, a targeted uveitis (syphilis, tuberculosis, sarcoidosis, BRC, cysticercosis) work-up was performed, which was negative, and treatment with 0.8mg/kg oral methylprednisolone was initiated. This treatment yielded no benefit after 1 month and was discontinued.
Over the ensuing months, BCVA dropped further to 20/50 in the right eye, and 20/32 in the left. Gene panel results showed a heterozygous pathogenic variant in the KCNV2 gene, and a variant of unknown significance in the TSPAN12 gene. These findings did not help establish a molecular diagnosis of RP. Scarce perivascular IPMs had appeared in the retinal periphery. Given the absence of RVL and CME improvement with corticosteroids, alongside compatible ancillary examination findings, a formal clinical diagnosis of RP was made.
The dual nature of the disease was explained to the patient (RP with inflammatory features, or possible associated non-infectious PU), and she agreed to a stepladder immunosuppressive approach.
Treatment for CME and RVL was then initiated with inconsistent responses. This included oral methylprednisolone, oral MTX, DEX IVT, and subcutaneous adalimumab, before ultimately obtaining CME and RVL control using IV TCZ 8mg/kg every 4 weeks (Fig. 1, S – V).
At the last follow-up, macular SD-OCT remained dry under IV TCZ 8mg/kg every 4 weeks. Final BCVA was 20/32 in the right eye, and 20/40 in the left.