Kazemi, Arash

Précis: In our study of the factors predictive of latanoprost response, we found that normotensive subjects with higher intraocular pressure, lower uveoscleral outflow, and higher body mass index had a greater response to 1-week treatment. Purpose: To evaluate relationships between variable intraocular pressure (IOP) responses to latanoprost and participant characteristics, baseline values and changes in aqueous humor dynamics (AHD) parameters. Methods: We assessed 226 eyes from 113 healthy participants. AHD parameters measured at baseline and after 1-week treatment with latanoprost included: IOP by pneumatonometry, episcleral venous pressure (EVP) by venomanometry, aqueous humor flow rate by fluorophotometry, outflow facility by 2-minute pneumatonography, and uveoscleral outflow calculated using the modified Goldmann equation. IOP responses were categorized into 4 groups: nonresponders (<10% reduction), all-responders (≥10% reduction), medium-responders (10%–20% reduction), and high-responders (≥20% reduction). Generalized estimating equation models were used to analyze treatment effects and compare groups. Results: Baseline IOP was higher in high-responders than medium-responders and nonresponders ( P =0.007 and P <0.001, respectively). Body mass index (BMI) was significantly higher in high-responders and all-responders compared with nonresponders ( P =0.02 and P =0.03, respectively). Responders had lower baseline uveoscleral outflow ( P =0.03). There were no significant differences in other baseline characteristics including EVP, outflow facility, and aqueous flow rate between the 4 groups. IOP decreased while outflow facility and uveoscleral outflow increased after latanoprost treatment in all responder groups but did not change in nonresponders. EVP and aqueous flow rate did not change significantly in any group. The change in uveoscleral outflow was greater in high-responders than in nonresponders ( P =0.004). Conclusions: In healthy subjects, higher baseline IOP, lower uveoscleral outflow and higher BMI are predictors of a greater IOP reduction by latanoprost. A greater increase in uveoscleral outflow is responsible for this larger response.

Purpose: To identify reasons for variable intraocular pressure (IOP) responses to latanoprost and timolol in healthy volunteers and to generate the control group as part of Eye Dynamics and Engineering Network. Methods: In this multicenter, randomized, crossover study (NCT01677507), both eyes of 106 healthy subjects (212 eyes) were treated with latanoprost or timolol for 7 days, with a 6-week washout between treatments. Ocular biometrics, tonometry, and aqueous humor dynamics (AHD) were assessed at baseline and day 8 of each treatment. Subjects were divided into responders and nonresponders using cutoffs of >15% or >10% IOP reduction. Treatment effects and correlations were analyzed with paired t-tests. Results: More subjects responded to latanoprost (54%) than timolol (27%) at >15% cutoff ( p < 0.01). Responders had higher mean baseline IOP than nonresponders for both drugs at both cutoffs ( p < 0.01). Among timolol nonresponders ( n = 56), 39% responded to latanoprost in both eyes, 20% in one eye, and 41% in neither. Among latanoprost nonresponders ( n = 31), 13% responded to timolol in both eyes, 13% in one eye, and 74% in neither. Latanoprost increased uveoscleral outflow, while timolol reduced aqueous flow and outflow facility. Low baseline uveoscleral outflow was associated with latanoprost response. Conclusions: Higher baseline IOP predicted better responses to both drugs. Higher baseline uveoscleral outflow predicted nonresponse to latanoprost. No AHD differences were linked to the timolol response. Timolol nonresponders were often responsive to latanoprost, but not vice versa.

Glaucoma is the leading cause of irreversible blindness worldwide. Ocular biomechanical properties have been implicated in glaucoma pathogenesis, but existing commercial devices cannot determine changes in specific tissues. We recently performed a study to compare corneal wave speed (a measure of corneal elasticity) and ocular rigidity (a whole eye measurement of ocular biomechanics) between glaucomatous and normal eyes. Twenty glaucomatous eyes from 10 patients and 20 normal eyes from 13 controls, matched for age, intraocular pressure (IOP), and axial length were included. Ocular rigidity was calculated based on the difference in supine IOP by pneumatonometry with and without a 10-g weight. Corneal wave speed was determined by ultrasound surface wave elastography in which a small, 0.1 s harmonic vibration at 100 Hz was generated through the closed eyelids. Wave propagation was captured by an ultrasound transducer, and wave speed was determined from the phase change with distance. No significant differences in corneal wave speed between glaucomatous and normal eyes were detected (P = 0.17). However, ocular rigidity was significantly lower in glaucomatous eyes (0.0218 ± 0.0033 vs 0.0252 ± 0.0050 μl−1, P = 0.01). While lower ocular rigidity is consistent with altered biomechanics in glaucoma, the lack of a difference in corneal wave speed suggests that corneal tissue may not be significantly affected, and scleral changes likely play a more important role.

Papilledema is optic nerve swelling caused by increased intracranial hypertension, which has the potential to cause significant vision loss. Papilledema from idiopathic intracranial hypertension (IIH) is typically bilateral and symmetric, but can sometimes be asymmetric and even unilateral. The cause for this asymmetry is unknown. The purpose of this study was to develop ultrasound vibro-elastography (UVE) for assessing patients with papilledema to evaluate for biomechanical differences in these eyes. Nine patients with papilledema from IIH and 9 age-matched healthy control subjects were enrolled. A local harmonic vibration was used to generate wave propagation through the eyelid. Three excitation frequencies of 100, 150, and 200 Hz were used. A 6.4 MHz ultrasound probe was used to measure wave propagation in the eye structures. Wave speeds were measured in the posterior sclera of the maculae. The magnitudes of the wave speed of the IIH patients’ posterior sclera were significantly higher than those of healthy subjects. In patients with unilateral papilledema, the wave speed of the posterior sclera were higher in the eyes with papilledema than in the contralateral eyes without papilledema. UVE provides a noninvasive technique to measure the wave speed of posterior sclera, which is stiffer in eyes with papilledema.