Inner Retinal Thinning in Hydroxychloroquine Therapy Does Not Trigger Functional Vision Loss, JIPMER Study
A recent cross-sectional study shows that while long-term hydroxychloroquine therapy causes significant structural thinning of the inner retina—evidenced by a reduced GC-IPL thickness of 77.0 ± 5.5 µm compared to 82.0 ± 5.3 µm in controls—this anatomical damage does not immediately trigger detectable functional vision loss, as published in the Indian Journal of Ophthalmology in May 2025.
Traditional hydrox7ychloroquine (HCQ) screening typically focuses on late-stage RPE and photoreceptor damage, yet research suggests ganglion cells are affected much earlier. To address the clinical gap between early structural loss and actual vision impairment, Dr. Shreyas Temkar and colleagues investigated the correlation between structural and functional integrity within the ganglion cell complex (GCC).
Therefore, the cross-sectional study compared 15 patients on long-term hydroxychloroquine (>5 years) with 15 healthy controls using SD-OCT and pattern ERG to assess retinal structure and function. To isolate the drug's impact, researchers excluded participants with high refractive errors, significant cataracts, or pre-existing optic nerve disease.
Key Clinical Findings of the Study Includes:
Significant Macular Thinning: The investigation revealed a markedly lower average GC-IPL thickness in the treatment group (77.0 ± 5.5 µm) compared to the control group (82.0 ± 5.3 µm).
Reduced Peripapillary Nerve Fiber Layer: Patients on long-term therapy showed a significantly thinner average retinal nerve fiber layer (RNFL) of 86.7 ± 9.6 µm, whereas the healthy controls maintained a thickness of 94.8 ± 7.6 µm.
Superior Quadrant Vulnerability: A localized reduction was specifically noted in the superior quadrant of the nerve fiber layer, which measured 105.2 ± 16.7 µm in cases versus 120.0 ± 15.6 µm in controls.
Minimal Functional Correlation: Despite clear structural loss, the study noted that functional parameters, such as the N95 implicit times on electrophysiology and visual field (VF) mean deviation scores, did not show statistically significant differences between the two groups.
The results suggest that although long-term hydroxychloroquine use is associated with undeniable structural changes in the inner retina, including a minimum GC-IPL thickness of 71.0 ± 8.1 µm in patients, these anatomical findings do not yet manifest as significant clinical functional dysfunction on routine tests.
Thus, the study concludes that clinicians may consider incorporating ganglion cell complex thickness measurements into their standard screening protocols to monitor for early signs of drug-related changes, yet they should remain cautious and not discontinue hydroxychloroquine based solely on inner retinal thinning in the absence of other established toxicity markers.
While the study provides valuable insights, its cross-sectional nature and small sample size highlight the need for larger, longitudinal research projects to better understand the long-term clinical implications and the potential for functional decline following early structural changes in the ganglion cell complex.
Reference
Temkar S, Mairal AT, Sahi A, Deb AK, Kavadichanda CG, Kaliaperumal S, et al. Structural and functional assessment of ganglion cell complex in patients on long-term hydroxychloroquine. Indian J Ophthalmol 2025;73:708-12.
