Current State of Quantitative Research on Upper Eyelid Sulcus Deepening with Prostaglandin Analogs
Quantitative research on the depth of upper eyelid sulcus deepening associated with prostaglandin analog therapy has been conducted and published, with specific measurements of adipocyte density changes demonstrating the mechanism and frequency of this adverse effect.
Evidence of Quantitative Studies
The most rigorous quantitative evidence comes from histopathological analysis measuring adipocyte density in orbital fat:
In monocular users of prostaglandin analogs, treated eyes showed significantly increased mean adipocyte density of 1758.21 ± 158.15 cells/mm² compared to 1258.73 ± 127.54 cells/mm² in untreated eyes (P = 0.04), confirming fat atrophy as the mechanism 1
Bimatoprost-treated eyes demonstrated the highest adipocyte density at 2073.35 ± 184.89 cells/mm², followed by travoprost at 1623.46 ± 218.99 cells/mm², both significantly different from untreated eyes (P < 0.001) 1
Latanoprost showed adipocyte density of 1468.20 ± 113.44 cells/mm², which was not significantly different from untreated eyes (P = 0.75) 1
Frequency Data Across Different Prostaglandin Analogs
A large prospective study of 250 patients quantified the frequency of upper eyelid sulcus deepening:
- Bimatoprost caused the highest frequency at 60% objective and 40% subjective occurrence 2
- Travoprost caused 50% objective and 24% subjective occurrence 2
- Latanoprost caused 24% objective and 12% subjective occurrence 2
- Tafluprost caused 18% objective and 10% subjective occurrence 2
- Unoprostone caused 8% objective and 10% subjective occurrence 2
The difference between bimatoprost and latanoprost, tafluprost, or unoprostone was statistically significant (P<0.001) 2
FDA Recognition
The FDA drug label for bimatoprost officially recognizes this adverse effect in postmarketing surveillance, listing "periorbital and lid changes associated with periorbital fat atrophy leading to skin tightness, deepening of the eyelid sulcus, eyelid ptosis, enophthalmos and eyelid retraction" 3
Reversibility Studies
Quantitative recovery data exists for switching from bimatoprost to latanoprost:
- Among 15 patients who developed deepening of upper eyelid sulcus on bimatoprost, 85% (11 of 13) showed decreased or resolved symptoms within 2 months of switching to latanoprost 4
- This improvement was maintained for at least 6 months 4
- Similar recovery was documented in case reports where 3 of 4 patients had resolution 2-3 months after switching from travoprost or bimatoprost to latanoprost 5
Clinical Implications
The quantitative research clearly establishes that bimatoprost carries the highest risk for upper eyelid sulcus deepening through measurable periorbital fat atrophy, occurring in approximately 60% of patients, which is significantly higher than latanoprost at 24% 2, 1