The report published by D. Damla Sevgi et al. represented five patients who presented with RP-like retinal pigmentary changes which were eventually attributed to longstanding uveitis. This study demonstrates that uveitis can mimic RP in atypical cases. Described patients were in age from 33 to 66 years old. Retinal pigmentary changes were bilateral in three cases and unilateral in two cases. All patients had negative family history. In differential diagnosis between RP and RP-like retinal pigmentary changes the authors relied on significant retinal vascular leakage or deep multifocal leakage on FA, which is significantly more common in uveitis than inherited retinal diseases. Also, authors got good response to steroids or other immunomodulators which testified towards uveitis. And another clue to the uveitis authors identified as perivascular pigmentation localization [21].
Of course, we considered possibility of RP-like mimicking uveitis. But in our cases patients were much younger (19 to 37 years vs. 33 to 66). RP changes were bilateral. They had complaints of visual fields impairment, bad mesopic and night vision more than 3 years (4 of them even more than 10 years). Herewith they developed complaints of deterioration in central vision only over the past year. All patients had typical for RP impairment in ERG. Also, all patients met criteria of typical RP fundus changes (retinal vessel attenuation, waxy pallor optic disc, and bone spicule pigmentation [11]). Pigmentation didn’t have perivascular localization. So, we didn’t suggest retinal changes as consequence of uveitis and tilt toward coexistence RP and uveitis.
As for the etiology of uveitis, then the data we obtained differ from previously studies. In the study conducted by Chowers I. et al on 338 patients with RP was found that 4 patients (1.2%) had the typical findings of FHU [6]. The largest study on this issue was conducted by Parthopratim et al, who analyzed 8364 PR-patients in more than 30 years period. They found out uveitis in 32 eyes of 22 RP-patients, so the prevalence of uveitis in RP-patient was 0.26%. The anterior uveitis was the most common in their study (18 eyes), followed by intermediate uveitis (14 eyes). Authors defined that among 18 eyes with anterior uveitis, 5 had typical feature of FHU and 3 eyes presented with acute nongranulomatous anterior uveitis [9]. In turn we diagnosed intermediate uveitis in all our patients, and 3 of them also had anterior uveitis. In general, the majority of reports about RP association with uveitis focused on FHU. These reports are not so large like mentioned above [3, 8, 16, 20, 25, 26, 27]. None of our patients had signs of FHU and all cases were bilateral. We revealed HLA-B27 antigen in 5 patients, and 2 of them were diagnosed ankylosing spondylitis after further investigations. Early diagnosis in these patients made it possible to prescribe systemic therapy timely and will help to avoid serious complications in the future.
We did not find any publications on the HLA-B27 positive uveitis associated with RP. The study on HLA typing in RP conducted in 1981 revealed no significant difference in the frequency of any HLA (A, B, C) antigen, when comparing autosomal dominant and recessive RP patients with a control population [15]. The study was conducted on 173 patients, and it obvious that patients with uveitis were not included in the study, so our data do not go against this study.
Concerning the remaining 2 patients with uveitis of unknown etiology, we cannot exclude that vitritis was a manifestation of the inflammatory reaction in RP. These data are consistent with Yoshida N. et al paper. They reported occasional or more cells in the vitreous cavity in 61.5% (313 eyes) of 509 eyes with RP; 1+ or more cells in 37.3% (190 eyes). Authors also detected increased levels of a variety proinflammatory cytokines and chemokines in the aqueous humor and vitreous fluid of RP patients. Authors supposed that sustained chronic inflammatory reaction occurs in patients with RP and is closely related to the disease pathogenesis [28].
Parthopratim Dutta Majumder et al emphasize that majority of the patients tend to have milder inflammation in anterior chamber and vitreous and are usually asymptomatic which might be a reason of hypodiagnostic. In their study only three RP-patients had prominent symptoms of acute uveitis [9]. Either in our series there were no acute uveitic patients. It’s very important to remember that in RP patient’s uveitis has a tendency to non-acute manifestation, and try not to miss the mild symptoms of uveitis.
Our study naturally has limitations. The main are absence of genetic analysis in RP patients, number of patients and not long duration of study. In addition, The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine is a tertiary referral center, so there is a potential bias toward more rare diseases. But in this case, it may even be advantage. Since uveitis and PR are orphan diseases and many cases from the whole country are referred to us.
Both treatment of RP and uveitis remain challenge. Treatment approaches include stem cell therapy, gene therapy and retinal implant, but the effectiveness of these methods in some cases is doubtful, many methods are under development and quite expensive.
Various methods for management of RP-associated CME includes oral and topical carbonic anhydrase inhibitors, oral, topical, intravitreal and periocular steroids, topical non-steroidal anti-inflammatory medications, laser photocoagulation, vitrectomy with internal limiting membrane peeling, oral lutein and intravitreal antivascular endothelial growth factor injection but there are no studies yet providing high-level evidence for RP-CME treatments [2, 10, 23]. In our case series we focused on the treatment of uveitis and the treatment of macular edema as its complication. In view of this, 3 patients were prescribed for systemic immunosuppressive drugs and 5 patients got STI. On the prescribed treatment the results were quite good with decrease in uveitis activity, BCVA improvement and complete CME resolving in 1 patient and partially resolving in other patients. Of course, this is a rather short observation period and further studies are required to evaluate the treatment modalities for uveitis in RP patients.