In vivo assessment of the ocular biomechanical properties in patients with idiopathic normal pressure hydrocephalus

**Background:** Idiopathic normal pressure hydrocephalus (iNPH) is a neurological syndrome characterized by gait dysfunction, cognitive impairment, and urinary incontinence, with enlarged ventricles but normal intracranial pressure (ICP). iNPH patients have a higher prevalence of open-angle glaucoma (OAG), possibly due to changes in the trans-laminar cribrosa pressure gradient (TCPG) between intraocular pressure (IOP) and ICP. Ocular biomechanics, particularly corneal hysteresis (CH), influence the behavior of the lamina cribrosa (LC). Lower CH is associated with faster glaucoma progression. This study aimed to compare ocular biomechanical properties between non-shunted iNPH patients and healthy controls using the Ocular Response Analyzer (ORA).

**Methods:** Twenty-four eyes of 24 non-shunted iNPH patients (median age 75.5 years, 29.2% female) and 25 eyes of 25 healthy age-matched controls (median age 75 years, 40% female) were prospectively recruited from November 2021 to February 2023. iNPH patients met “probable” iNPH criteria per Relkin et al. guidelines and were eligible for VP shunt surgery. Exclusion criteria included ocular trauma, retinal detachment, corneal opacities, advanced cataract, high myopia (< -6 D) or hyperopia (> +3 D), axial length >26 mm or <21 mm, uveitis, pachymetry <450 μm or >650 μm, prior glaucoma diagnosis, ocular hypertension, or previous laser/antiglaucoma treatment. All participants underwent comprehensive ophthalmic examination including BCVA, refraction, slit lamp exam, indirect ophthalmoscopy, axial length (AL) and central corneal thickness (CCT) measurements (IOLMaster 700). ORA measurements were performed by masked operators between 10 am and 12 pm to control for diurnal IOP variation. CH, CRF, IOPg, and IOPcc were recorded. Only measurements with waveform score >7.0 were included; the best of 4 measurements was used. Right eyes were analyzed. Non-parametric tests (Mann-Whitney, Chi-square) were used; p<0.05 was significant.

**Key Results:** Demographics were comparable between groups (age p=0.711, sex p=0.551, pseudophakia p=0.702). Clinical parameters (BCVA, SE, CCT, AL) showed no significant differences. CH was significantly lower in iNPH patients (median 9.7 mmHg, IQR 7.82–10) vs. controls (median 10.6 mmHg, IQR 9.3–11.3; p=0.015). No significant differences were found in IOPcc (iNPH: median 18.1 mmHg, IQR 14.72–19.92; controls: 16.4 mmHg, IQR 13.05–19.6; p=0.150), IOPg (iNPH: 15.4 mmHg, IQR 12.82–19.7; controls: 15.3 mmHg, IQR 12.55–17.35; p=0.610), or CRF (iNPH: 9.65 mmHg, IQR 8.07–11.65; controls: 10.3 mmHg, IQR 9.3–11.5; p=0.412). Waveform scores were similar (p=0.100).

**Clinical Implications:** The significantly lower CH in iNPH patients suggests reduced ocular viscoelastic damping ability, potentially indicating stiffer LC and peripapillary sclera. This may increase susceptibility to glaucomatous optic nerve damage from IOP or ICP fluctuations. Since CH is a surrogate biomarker for posterior ocular tissue biomechanics, lower CH could help explain the higher OAG prevalence in iNPH. The study recommends routine IOP assessment at iNPH diagnosis and possibly targeting lower IOP values to reduce glaucoma risk. Additionally, after VP shunt surgery, ICP should not be excessively lowered to avoid increasing TCPG. Limitations include small sample size and inclusion of only pre-shunt patients. Future studies should compare pre- and post-shunt biomechanics and assess CH in glaucomatous vs. non-glaucomatous iNPH patients.