Post-COVID Ocular Syndrome
1 Moustardas et al. 2026 — Long-Term Ocular Symptoms After COVID-19
Full Citation:: Moustardas P, Setterud H, Meijer H, Andersson G, Roth J, Dashti A, Johansson B, Macedo AF, Lagali N. Long-term ocular symptoms following COVID-19 linked to immune dysregulation, dysautonomia and peripheral neuropathy. Nature Communications. 2026;17(1):5624. (Moustardas et al. 2026) DOI:: 10.1038/s41467-026-74858-4 PMID:: 42420292 Published:: July 8, 2026 Study Design:: Prospective cross-sectional observational study Sample Size:: n=100 non-hospitalised post-mild-COVID patients with persistent ocular symptoms (3mo–3yr), n=32 mild-COVID controls without ocular symptoms Key Findings::
- 1 in 3 patients on full/part-time sick leave due to ocular disability
- Standard ophthalmic exams (visual acuity, slit-lamp, fundoscopy) normal; abnormalities only on specialised testing
- Near vision disturbances, adult-onset strabismus, weakened autonomic pupillary reflexes, corneal neurodegeneration (reduced nerve fiber density), chronic activation of ocular surface dendritic/T cells (corneal confocal microscopy)
- Tear fluid proteomics: abnormal pattern of nerve-regulating and T-cell-regulating proteins; same protein pattern found in blood/tissue of severe/fatal COVID (other studies)
- Upregulation of ITGB6, NFASC, CTGF, TPSAB1, CKMT1A-CKMT1B
- Pupil dysfunction correlated with elevated JUN; dendritic/T-cell dysregulation correlated with ANGPTL2, SKAP2, DAPP1
- Two diagnostic models proposed: instrument-only (eye clinic measurements, ~77% accuracy) and instrument + tear proteomics (~91% accuracy)Conclusion:: Post-COVID ocular syndrome is a debilitating condition driven by immune dysregulation, dysautonomia, and peripheral neuropathy manifesting in the eye. Tear proteomics implicates chronic T-cell-mediated neuroinflammation. Requires specialised testing for diagnosis; standard ophthalmic exams are insufficient. Limitations:: Cross-sectional design; single center (Linköping, Sweden); non-hospitalised cohort only; no ME/CFS subgroup analysis; controls were mild-COVID without ocular symptoms (not infection-naïve). Diagnostic models need external validation. ME/CFS Relevance:: Directly demonstrates small-fiber neuropathy, dysautonomia, and immune dysregulation in a post-COVID cohort. The tear proteomic signature (T-cell dysregulation, nerve-regulatory proteins) parallels mechanisms implicated in ME/CFS. Documented corneal nerve degeneration provides accessible tissue-level window into small-fiber pathology shared with ME/CFS. Self-report photophobia + accommodation deficits overlap with ME/CFS cognitive/visual symptoms. Certainty Assessment::
- *Quality:* High (Nature Communications; prospective; multimodal: clinical, imaging, proteomics, diagnostic modeling)
- *Sample:* Medium (n=132 total; n=100 POS, n=32 controls)
- *Replication:* Single study — not yet independently replicated
- *Score:* 0.752 Smit et al. 2026 — Altered Pupillary Dynamics in Post-COVID Syndrome
Full Citation:: Smit A, Fleischmann P, Knauer TS, Mardin CY, Michelson G, Zott J, Güttes M, Sarmiento H, Ilgner M, Jakobi M, Rech J, Hohberger B. Task-evoked pupillary dynamics are altered in post-COVID syndrome. Medical Sciences. 2026;14(2):269. (Smit et al. 2026) DOI:: 10.3390/medsci14020269 PMID:: 42201061 Study Design:: Cross-sectional pupillometry study using VR-based stereoscopic task Sample Size:: n=397 PCS patients, n=129 healthy controls Key Findings::
- Index of Pupillary Activity (IPA) significantly lower in PCS at all three task difficulty levels ($\beta = -0.111$, 95% CI $-0.160$ to $-0.062$, $p < 0.001$)
- Low/High IPA (LHIPA) also significantly lower ($\beta = -0.164$, 95% CI $-0.253$ to $-0.074$, $p < 0.001$)
- Lower task difficulty associated with higher pupillary metrics (inverse difficulty-IPA relationship)
- Age negatively associated; male sex positively associated
- No significant interaction between cohort and task difficultyConclusion:: Post-COVID syndrome is associated with reduced task-evoked pupillary dynamics, suggesting altered autonomic regulation of pupillary function that may serve as objective marker for cognitive-load processing deficits. Limitations:: Cross-sectional; single VR-based task; PCS diagnosis per self-report without laboratory confirmation; IPA/LHIPA as surrogate markers require validation against clinical pupillometry standards. ME/CFS Relevance:: Directly demonstrates pupil dysfunction as objective marker of autonomic dysregulation in a post-infectious syndrome overlapping with ME/CFS. Complements Moustardas 2026 pupillary findings with a larger cohort and quantitative task-evoked paradigm. Supports pupillometry as non-invasive biomarker for autonomic dysfunction. Certainty Assessment::
- *Quality:* Medium (peer-reviewed, large n, controlled design)
- *Sample:* Large (n=526)
- *Replication:* Single study with novel methodology
- *Score:* 0.653 Johansson et al. 2022 — Visual Function in Post-COVID Neurorehabilitation
Full Citation:: Johansson J, Levi R, Jakobsson M, Gunnarsson S, Samuelsson K. Multiprofessional neurorehabilitation after COVID-19 infection should include assessment of visual function. Archives of Rehabilitation Research and Clinical Translation. 2022;4(2):100184. (Johansson et al. 2022) DOI:: 10.1016/j.arrct.2022.100184 PMID:: 35434699 Study Design:: Cross-sectional observational study in neurorehabilitation setting Key Findings::
- High prevalence of convergence insufficiency and accommodative dysfunction in post-COVID patients referred for neurorehabilitation
- Visual processing deficits contributing to reading difficulty, concentration problems, and fatigue
- Visual symptoms often overlooked in standard post-COVID assessment protocolsConclusion:: Visual function assessment should be routinely included in post-COVID neurorehabilitation. Limitations:: Small sample; referral bias (neurorehabilitation population); no control group; not specific to ocular sequelae of COVID-19 vs. general post-viral visual dysfunction. ME/CFS Relevance:: Documents convergence insufficiency and accommodative dysfunction in post-COVID patients — the same near-vision deficits that Moustardas 2026 found to be hallmark features of post-COVID ocular syndrome. Supports the eye muscle nerve-control hypothesis (cranial nerve III/IV/VI involvement in post-infectious dysautonomia). Certainty Assessment::
- *Quality:* Low-Medium (small, uncontrolled, rehabilitation setting)
- *Sample:* Small
- *Score:* 0.404 Naseri et al. 2025 — Dry Eye Disease Post-COVID: Systematic Review
Full Citation:: Naseri A, Fard MA, Zarei M, Jabbarvand M, Taheri F. Prevalence and risk factors of dry eye disease after COVID-19: a systematic review and meta-analysis. International Ophthalmology. 2025;45(1):134. (Naseri et al. 2025) DOI:: 10.1007/s10792-025-03532-9 Study Design:: Systematic review and meta-analysis Key Findings::
- Pooled prevalence of dry eye disease significantly elevated after COVID-19
- Risk factors: female sex, acute disease severity, longer recovery period
- Dry eye symptoms persisted in a substantial subset beyond 6 monthsConclusion:: Dry eye disease is a common long-term ocular complication of COVID-19. Limitations:: Heterogeneity across included studies; publication bias possible; limited longitudinal data. ME/CFS Relevance:: Establishes the prevalence of ocular surface disease post-COVID, providing epidemiological context for Moustardas 2026 findings. Dry eye in ME/CFS may share similar mechanisms (autonomic dysfunction reducing lacrimal secretion, neuroinflammation affecting corneal nerves). Certainty Assessment::
- *Quality:* Medium (systematic review/meta-analysis)
- *Sample:* Large (pooled across studies)
- *Replication:* Multiple studies included
- *Score:* 0.55