Dose–Response Structural And Spectral Changes In Hydrophobic Intraocular Lenses Following Exposure To Topical Glaucoma Medications

Pseudophakia and chronic glaucoma therapy frequently coexist, exposing intraocular lenses (IOLs) to long-term topical hypotensive medications. Prior in vitro work has demonstrated that hypotensive drugs, including dorzolamide and timolol, induce discoloration, precipitate formation, and altered light absorbance in IOLs. However, wavelength-specific and concentration-dependent effects in hydrophobic IOLs remain incompletely characterized. This study aimed to evaluate dose–response structural alterations and spectral absorbance changes in two hydrophobic IOL models following graded exposure to timolol and dorzolamide.

An experimental laboratory study was conducted in a controlled research facility using accelerated aging conditions to simulate long-term drug exposure to implanted hydrophobic intraocular lenses.

Two hydrophobic IOL models (E and J) were immersed in six graded concentrations (12.5%–100%) of timolol maleate 0.25% and dorzolamide 2%; balanced salt solution served as control. Samples were incubated at 82°C for one year. Precipitation and discoloration were assessed using 40× surgical microscopy and 100× light microscopy. Light absorbance (410–680 nm) was measured centrally. Full-spectrum dose–response relationships were analyzed using Pearson correlation, with Spearman rank correlation as a monotonicity check (n=126 pooled measurements per condition). A three-factor ANOVA assessed the effects of drug, IOL type, and wavelength on correlation coefficients.

Seventy-eight IOLs completed incubation. Dorzolamide demonstrated concentration-dependent precipitation and discoloration in both IOLs and modest positive correlations regarding light absorbance across all wavelengths, reaching significance at 410 nm in IOL E. Timolol demonstrated consistent negative correlations regarding light absorbance across 410–500 nm and 680 nm in both IOLs, with weaker or absent effects at 550–580 nm in IOL J. Full-spectrum analysis strengthened these findings: Dorzolamide showed modest positive dose–response (E: r=0.205, p=0.022; J: r=0.308, p<0.001), Timolol showed significant inverse associations (E: r=−0.588, p<0.001; J: r=−0.253, p=0.004). ANOVA identified drug type as the only significant factor (p<0.0001). 

Topical glaucoma medications produced drug-specific structural and spectral effects in hydrophobic IOLs under accelerated conditions. Dorzolamide was associated with modest concentration-dependent precipitation, discoloration, and increased absorbance, whereas timolol demonstrated a consistent inverse spectral dose–response without clear structural deposition. Drug type appears to be the dominant determinant of spectral change. Although in vitro, these findings suggest potential medication–material interactions that may influence long-term optical performance. Clinicians should remain aware of possible IOL–drug interactions and apply clinical discretion when selecting long-term hypotensive therapy in pseudophakic patients.