Omidenepag Isopropyl Versus Timolol in Patients With Glaucoma or Ocular Hypertension: Two Randomized Phase 3 Trials (SPECTRUM 4 and 3).

PURPOSE: The SPECTRUM 4 and 3 studies assessed the intraocular pressure (IOP)-lowering efficacy and safety of omidenepag isopropyl (OMDI) 0.002% vs timolol 0.5% in patients with glaucoma or ocular hypertension (OHT). DESIGN: Phase 3, randomized, controlled, double-masked, noninferiority studies. METHODS: Multicenter studies in the US. Inclusion criteria for adults ≥ 18 years (SPECTRUM 4 [N = 409] and 3 [N = 413]) were open-angle glaucoma or OHT, and IOP ≥ 22 mm Hg and ≤ 34 mm Hg; and for pediatric patients < 18 years (N = 13, SPECTRUM 3) were pediatric glaucoma or OHT. The primary objective in both studies was OMDI noninferiority to timolol in reducing IOP (3 months). SPECTRUM 3 included an additional 9 months of OMDI treatment. Safety evaluations were of ocular/non-ocular adverse events (AEs). RESULTS: The IOP-lowering range of OMDI remained consistent in SPECTRUM 4 and 3 (-5.6 to -5.9 vs -5.3 to -5.7 mm Hg, respectively); however, timolol efficacy varied (-5.4 to -6.1 vs -6.4 to -7.0 mm Hg, respectively). OMDI noninferiority was achieved in SPECTRUM 4. Efficacy was maintained with 12-month treatment in SPECTRUM 3. Both studies reported more ocular AEs with OMDI, but lower rates of appearance-altering AEs vs timolol. No new safety concerns were identified. Rates of macular edema in pseudophakic patients increased with prolonged OMDI exposure. CONCLUSIONS: SPECTRUM 4 and 3 demonstrated consistent 3-month IOP-lowering efficacy and safety of OMDI vs timolol in patients with glaucoma or OHT. The 12-month data from SPECTRUM 3 suggest OMDI may have long-term benefits in patients with glaucoma or OHT.

FP and EP2 prostanoid receptor agonist drugs and aqueous humor outflow devices for treating ocular hypertension and glaucoma.

Prostaglandin (PG) receptors represent important druggable targets due to the many diverse actions of PGs in the body. From an ocular perspective, the discovery, development, and health agency approvals of prostaglandin F (FP) receptor agonists (FPAs) have revolutionized the medical treatment of ocular hypertension (OHT) and glaucoma. FPAs, such as latanoprost, travoprost, bimatoprost, and tafluprost, powerfully lower and control intraocular pressure (IOP), and became first-line therapeutics to treat this leading cause of blindness in the late 1990s to early 2000s. More recently, a latanoprost-nitric oxide (NO) donor conjugate, latanoprostene bunod, and a novel FP/EP3 receptor dual agonist, sepetaprost (ONO-9054 or DE-126), have also demonstrated robust IOP-reducing activity. Moreover, a selective non-PG prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI), was discovered, characterized, and has been approved in the United States, Japan and several other Asian countries for treating OHT/glaucoma. FPAs primarily enhance uveoscleral (UVSC) outflow of aqueous humor (AQH) to reduce IOP, but cause darkening of the iris and periorbital skin, uneven thickening and elongation of eyelashes, and deepening of the upper eyelid sulcus during chronic treatment. In contrast, OMDI lowers and controls IOP by activation of both the UVSC and trabecular meshwork outflow pathways, and it has a lower propensity to induce the aforementioned FPA-induced ocular side effects. Another means to address OHT is to physically promote the drainage of the AQH from the anterior chamber of the eye of patients with OHT/glaucoma. This has successfully been achieved by the recent approval and introduction of miniature devices into the anterior chamber by minimally invasive glaucoma surgeries. This review covers the three major aspects mentioned above to highlight the etiology of OHT/glaucoma, and the pharmacotherapeutics and devices that can be used to combat this blinding ocular disease.

Phase 2b, Randomized, 3-Month, Dose-Finding Study of Sepetaprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: The ANGEL Study.

Purpose: This phase 2b, randomized, observer-masked, placebo- and active-controlled, parallel-group, multinational (USA and Japan), multicenter study (NCT03216902) assessed the optimal dose of sepetaprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension. Methods: After washout, patients ≥18 years (USA) or ≥20 years of age (Japan) received once-daily sepetaprost for 3 months [0.0005% (n = 43); 0.001% (n = 43); 0.002% (n = 44); and 0.003% (n = 45)], latanoprost 0.005% (n = 44) or placebo until week 6, followed by sepetaprost 0.003% until month 3 (n = 22). Safety assessments included adverse event (AE) occurrence. Results: Baseline mean diurnal intraocular pressure (IOP) was 24.3 mmHg for latanoprost and ranged between 24.1 and 24.5 mmHg for the sepetaprost groups. Sepetaprost 0.002% had the lowest IOP at each month 3 time point (9:00 AM; 1:00 PM; 5:00 PM) of all sepetaprost concentrations (mean ± standard error: 17.6 ± 0.5; 17.4 ± 0.4; 16.7 ± 0.4 mmHg); similar values were observed with latanoprost (18.1 ± 0.6; 17.3 ± 0.5; 17.2 ± 0.5 mmHg). A positive dose-response relationship was observed with the 3 lower sepetaprost doses; sepetaprost 0.002% had numerically greater IOP-lowering effects than sepetaprost 0.003%. All sepetaprost doses had statistically significantly greater IOP reductions from baseline versus placebo at week 6 (P < 0.0001). This IOP-lowering effect was consistent between Japan- and USA-based patients. Most AEs were mild and occurred numerically less frequently with sepetaprost 0.002% (34.1%) versus latanoprost (50.0%). The most frequently reported AE was conjunctival hyperemia. Conclusion: In this study, sepetaprost 0.002% was the optimal concentration, showing comparable IOP-lowering efficacy and safety with latanoprost 0.005%. Most AEs were mild; occurrence was numerically lower with sepetaprost 0.002% than latanoprost 0.005%.

Twelve-month efficacy and safety of omidenepag isopropyl, a selective EP2 agonist, in open-angle glaucoma and ocular hypertension: the RENGE study.

PURPOSE: To assess the long-term safety and efficacy of omidenepag isopropyl (OMDI) 0.002% (a first-in-class, selective, non-prostaglandin, prostanoid EP2 receptor agonist), alone or administered concomitantly with timolol 0.5%, in patients with open-angle glaucoma (OAG, including normal-tension and exfoliation glaucoma) or ocular hypertension (OHT). STUDY DESIGN: Open-label, multicenter, Phase 3 study (NCT02822729). METHODS: Patients aged ≥ 20 years, with OAG or OHT, and a baseline diurnal intraocular pressure (IOP) ≥ 16- < 22 mmHg (Group 1) or ≥ 22- ≤ 34 mmHg (Groups 2 and 3) were enrolled. All patients (N = 125) received OMDI 0.002% once daily. Group 3 also received timolol 0.5% twice daily. IOP was measured at baseline and at Weeks 2, 4, 8, 12, 26, 40, and 52. RESULTS: Significant reductions in mean diurnal IOP from baseline occurred at every visit (P < 0.0001). Mean ± SE diurnal IOP reduction at Week 52 was -3.7 ± 0.3 mmHg (Group 1), -5.6 ± 0.5 mmHg (Group 2), and -8.4 ± 0.6 mmHg (Group 3). Most adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Conjunctival hyperemia (incidence: monotherapy [Groups 1 and 2], 18.8%; concomitant [Group 3], 45.0%) and macular edema (ME)/cystoid macular edema (CME) (incidence: monotherapy, 11.8%; concomitant, 15.0%) occurred most frequently. All treatment-related ME/CME cases occurred in pseudophakic eyes and responded to standard-of-care treatment and study drug discontinuation. CONCLUSIONS: In this study, OMDI 0.002%, alone or administered concomitantly with timolol 0.5%, resulted in sustained IOP reduction over 52 weeks in patients with OAG or OHT. Concomitant treatment resulted in increased efficacy and increased incidence of conjunctival hyperemia.

A Randomized Phase 2 Trial Comparing Omidenepag Isopropyl 0.002% Once and Twice Daily in Subjects With Primary Open-angle Glaucoma or Ocular Hypertension (SPECTRUM-6).

PRCIS: No significant difference was found between the intraocular pressure (IOP) lowering of omidenepag isopropyl 0.002% once daily (QD) and twice daily (BID). However, adverse events (AEs) were higher in the BID arm; thus, QD dosing is the preferred dosing frequency for further investigation. PURPOSE: This phase 2, randomized, double-masked, parallel-arm, multicenter study (NCT03858894) was conducted in the United States to examine whether the efficacy and safety of omidenepag isopropyl 0.002% BID dosing was superior to QD dosing in subjects with primary open-angle glaucoma or ocular hypertension. METHODS: Randomized subjects (1:1) received omidenepag isopropyl 0.002% QD (n=50) or BID (n=48) for 6 weeks (after a ≤4-week washout period). IOP was measured at 8:00 am, 12:00 pm, and 4:00 pm at baseline and weeks 2 and 6. The primary efficacy endpoint was IOP at each timepoint at weeks 2 and 6. AEs were evaluated. RESULTS: Baseline mean diurnal IOP (±SD) post washout was 25.4±2.9 mm Hg (BID) and 24.6±1.9 mm Hg (QD). At weeks 2 and 6, clinically significant IOP reductions from baseline were observed for omidenepag isopropyl BID and QD treatments. Least-squares mean (±SE) IOP differences (BID versus QD) were not statistically significant (week 2: 0.44±0.68 to 1.08±0.65 mm Hg; week 6: 0.36±0.63 to 0.68±0.68 mm Hg) at any timepoint (all P > 0.05). AEs were 3-fold greater in the BID arm (41.7%; QD: 14.0%); the most frequently reported AE was conjunctival/ocular hyperemia (BID: 22.9%; QD: 2.0%). Five subjects discontinued omidenepag isopropyl prematurely, 4 of 5 owing to AEs (BID: 4; QD: 0). CONCLUSION: In this study, the benefit-risk profile of omidenepag isopropyl 0.002% QD was more favorable than the benefit-risk profile of BID. This difference was driven by a higher incidence of local tolerability issues in the BID arm.

Intraocular pressure-lowering effect of omidenepag isopropyl in latanoprost non-/low-responder patients with primary open-angle glaucoma or ocular hypertension: the FUJI study.

PURPOSE: Omidenepag isopropyl (OMDI) is the prodrug of omidenepag, a selective, non-prostaglandin, prostanoid EP2 receptor agonist, which has been shown to lower intraocular pressure (IOP) in patients with glaucoma and ocular hypertension (OHT). This study evaluated the efficacy and safety of OMDI ophthalmic solution 0.002% in patients with primary open-angle glaucoma or OHT who were non-/low responders to latanoprost. STUDY DESIGN: Open-label, multicenter, Phase 3 study (NCT02822742). METHODS: Following 1-4-week washout, patients were treated with latanoprost ophthalmic solution 0.005% during an 8-week run-in period. Patients with ≤15% IOP reduction at the end of the run-in (indicating non-/low response) received OMDI 0.002% (one drop once daily for 4 weeks). The primary endpoint was the change from baseline in mean diurnal IOP at Week 4. RESULTS: In total, 26 patients were treated with OMDI; two withdrew owing to lack of efficacy. The mean diurnal IOP at baseline (end of latanoprost run-in) was 23.1 mmHg (7.6% IOP reduction from end of washout) indicating non-/low response to latanoprost. After 4 weeks of OMDI treatment, mean diurnal IOP was significantly reduced from baseline (-2.99 mmHg; P < 0.0001). No serious adverse events were reported. Adverse events occurred in five patients (19.2%); adverse drug reactions (anterior chamber cell, conjunctival hyperemia, and erythema of eyelid) occurred in two patients (7.7%) and were mild in severity. CONCLUSIONS: In this study, OMDI 0.002% demonstrated a clinically significant reduction in IOP and was well tolerated in patients with primary open-angle glaucoma and OHT who were non-/low responders to latanoprost.

Omidenepag Isopropyl Versus Latanoprost in Primary Open-Angle Glaucoma and Ocular Hypertension: The Phase 3 AYAME Study.

PURPOSE: To evaluate the efficacy and safety of omidenepag isopropyl (OMDI), a selective, non-prostaglandin, prostanoid EP2 receptor agonist, in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). DESIGN: Phase III, randomized, investigator-masked, active-controlled, parallel-group, noninferiority study (ClinicalTrials.govNCT02623738). METHODS: After a washout period of 1-4 weeks, eligible patients were randomized (1:1) to OMDI 0.002% or latanoprost 0.005% once daily for 4 weeks. Intraocular pressure (IOP) was measured at 9:00 AM, 1:00 PM, and 5:00 PM at weeks 1, 2, and 4. The primary endpoint was the change from baseline in mean diurnal IOP at week 4. The noninferiority margin for OMDI versus latanoprost was 1.5 mm Hg. Adverse events (AEs) were recorded. RESULTS: Of the 190 patients randomized, 189 had at least 1 post-baseline IOP measurement. At baseline, patients who received OMDI or latanoprost had a mean ± SD diurnal IOP of 23.78 ± 1.73 mm Hg and 23.40 ± 1.51 mm Hg, respectively. At week 4, least-squares mean ± SE reduction in IOP from baseline with OMDI (-5.93 ± 0.23 mm Hg) was noninferior to that of latanoprost (-6.56 ± 0.22 mm Hg; 95% confidence interval between groups: 0.01-1.26). The most frequently reported treatment-related ocular AEs (OMDI vs latanoprost) were conjunctival hyperemia (23/94 patients [24.5%] vs 10/96 patients [10.4%]), corneal thickening (11/94 patients [11.7%] vs 1/96 patients [1.0%]), and punctate keratitis (0/94 patients vs 5/96 patients [5.2%]). No serious AEs were observed in either group, and there were no discontinuations related to the study drug. CONCLUSIONS: OMDI 0.002% was noninferior to latanoprost 0.005% in reducing IOP in patients with OHT or POAG and was well tolerated.

Pharmacokinetics, Safety, and Intraocular Pressure-Lowering Profile of Omidenepag Isopropyl, a Selective, Nonprostaglandin, Prostanoid EP2 Receptor Agonist, in Healthy Japanese and Caucasian Volunteers (Phase I Study).

Purpose: Omidenepag isopropyl (OMDI) is a prodrug of OMD, a selective, nonprostaglandin, prostanoid EP2 receptor agonist. This phase I study aimed to investigate the pharmacokinetic properties, safety, and intraocular pressure (IOP)-lowering efficacy of OMDI. Methods: Fourteen healthy male volunteers (7 Japanese and 7 Caucasian) 20-35 years of age received 1 drop of OMDI 0.0025% at 9:00 h in both eyes for 7 days. Blood samples were taken predose and up to 8 h postdose on days 1, 3, and 7. The plasma concentration of OMD was determined using high-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters measured included the maximum plasma concentration (Cmax) and the half-life (t½) of OMD. IOP, adverse events (AEs), ophthalmic examinations, vital signs, and laboratory values were assessed. Results:Cmax for all subjects was reached after 10-15 min and decreased with a t½ of ∼30 min. Ad hoc statistical analyses found significant differences in some pharmacokinetic parameters between Japanese and Caucasian subjects, likely due to differences in body weight. These differences reduced over 7 days of dosing and were not thought to be clinically meaningful. There was no OMD accumulation after 7 days of repeated dosing. Mean IOP was reduced by ∼4-5 mmHg between baseline and 2 h postdose, remaining stable from day 3 onward. All AEs were mild and considered treatment related. Conclusions: Pharmacokinetic parameters of OMD were similar between Japanese and Caucasian subjects. There was no accumulation of OMD after 7 days of dosing. OMDI was well tolerated and demonstrated clinically significant IOP reductions.

Phase 2, Randomized, Dose-finding Studies of Omidenepag Isopropyl, a Selective EP2 Agonist, in Patients With Primary Open-angle Glaucoma or Ocular Hypertension.

PRéCIS:: Three randomized, multicenter studies demonstrated the stable intraocular pressure-lowering effects and tolerability of omidenepag isopropyl in patients with primary open-angle glaucoma and ocular hypertension; 0.002% was identified as the optimal dose for further investigation. PURPOSE: The purpose of this study was to assess the safety and efficacy of omidenepag isopropyl, a selective EP2 agonist, and to determine the optimal dose for further investigation. PATIENTS AND METHODS: Three randomized, controlled, masked, multicenter studies were conducted in United States (study 1, NCT01868126; study 2, NCT02179008) and Japan (study 3, NCT02623738). Patients were randomized to 1 of 7 omidenepag isopropyl concentrations (0.0003%, 0.001%, 0.0012%, 0.0016%, 0.002%, 0.0025%, and 0.003%), latanoprost (0.005%), or placebo, 1 drop once daily for 28 days (studies 1 and 3) or 90 days (study 2). Primary endpoints were the observed mean diurnal intraocular pressure (IOP) and IOP at each time point on the final visit (studies 1 and 2) and change from baseline in mean diurnal IOP at week 4 (study 3). RESULTS: IOP-lowering effects of omidenepag isopropyl 0.0003% to 0.002% increased dose-dependently. Omidenepag isopropyl 0.002% and 0.0025% resulted in clinically relevant mean diurnal IOP reductions from baseline that were similar to those of latanoprost and superior to placebo (P<0.005). Maximum reductions had already been achieved by week 1, and stable IOP-lowering effects were observed at all postbaseline time points up to 3 months. Most adverse events (AEs) were mild. Conjunctival hyperemia was the most frequently reported AE, the incidence of which increased dose-dependently. The safety profiles of omidenepag isopropyl 0.002% and 0.0025% were similar, with a slightly lower incidence of AEs in the 0.002% group. CONCLUSIONS: Omidenepag isopropyl demonstrated stable IOP-lowering effects and was well tolerated; 0.002% was identified as the optimal dose for phase 3 investigation.

Corneal refractive therapy gas permeable lenses for the correction of hyperopia after one night of lens wear.

PURPOSE: To examine the refractive and keratometric response of corneal refractive therapy (CRT) contact lenses for hyperopia (CRT) after a single night of contact lens wear with the goal of reducing hyperopia by +3.50 D. METHOD: Twenty participants were fitted with a CRT HDS 100 contact lens, in one eye only. The back optic zone radius of the CRT lens was designed to correct 3.50 D of hyperopia. The eyes were randomly selected. The Nikon Auto Refractor was used to measure refractive error. Corneal topography and simulated K readings were measured using the Humphrey Atlas topographer. The lens was subsequently worn overnight, and the lens was assessed the next morning on awakening. RESULTS: Refractive error changed by 1.50±0.71 D (mean ± SD, range 0.50-2.75 D) immediately after lens removal in the experimental eye. Similarly, there was a change in flat K readings of 0.58±0.62 D with a range of -0.25 to +1.87 D. These results were significantly different from the baseline measurements (P<0.0001). CONCLUSIONS: The fitting of CRT HDS for hyperopia has a significant effect on corneal shape and refractive error. There was a moderate yet significant steepening of the cornea.

Malleability of the ocular surface in response to mechanical stress induced by orthokeratology contact lenses.

PURPOSE: To determine the malleability of the ocular surface by examining the acute effects of local mechanical stress on optical performance, corneal shape, and corneal/epithelial thickness after corneal refractive therapy for myopia and hyperopia (CRT and CRTH). METHODS: Twenty ametropes (spherical equivalent: -2.08 +/- 2.31 D) wore CRT and CRTH lenses in a random order on 1 eye (randomly selected). The lenses were worn for 15, 30, and 60 minutes (randomly ordered, with each period taking place on a different day). Refractive error, aberrations, corneal topography, and corneal/epithelial thickness (using OCT) were measured before and after lens wear. The measurements were performed on the control eyes at the 60-minute visit only. RESULTS: With both CRT and CRTH lens wear, significant changes occurred in many parameters from the 15-minute time point. The refractive error and defocus decreased after CRT lens wear (all P < 0.05) and increased after CRTH lens wear from baseline (all P < 0.05). Astigmatism did not change (both P > 0.05). Higher-order aberrations, including coma and spherical aberration (SA), increased after CRT and CRTH lens wear (all P < 0.05) from baseline, but the signed SA shifted from positive to negative after CRTH lens wear (P < 0.05). The central cornea flattened and the midperiphery steepened after CRT lens wear, whereas the central cornea steepened and paracentral region flattened after CRTH lens wear (P < 0.05). The central cornea swelled less than the midperiphery after CRT lens wear (P < 0.05), whereas the central cornea swelled more than the paracentral region after CRTH lens wear (P < 0.05). The central epithelium was thinner than the midperiphery after CRT lens wear (P < 0.05) and thicker than the paracentral region after CRTH lens wear (P < 0.05). Optical performance, corneal curvature, and epithelial thickness did not change from baseline in the control eyes (all P > 0.05). CONCLUSIONS: CRT lenses for myopia and hyperopia induce significant structural and optical changes in as little as 15 minutes. The cornea, particularly the epithelium, is remarkably malleable, with rapid steepening and flattening possible in little time.

The relationship between the treatment zone diameter and visual, optical and subjective performance in Corneal Refractive Therapy lens wearers.

PURPOSE: To investigate the stability of the treatment zone (TZ) size during Corneal Refractive Therapy (CRT) over 4 weeks of lens wear, and to determine the relationship between TZ diameter and visual, optical and subjective performance. METHODS: Twenty-three myopic subjects wore CRT lenses overnight and removed their lenses on awakening. Visual Acuity (VA), subjective vision, refractive error, aberrations and corneal topography were measured at baseline, immediately after lens removal on the first day and 14 h later, and these measurements were repeated on days 4, 10 and 28. The TZ including the central flattened zone (CFZ) and the annular steepened zone (ASZ) was demarcated by the change in corneal curvature from negative to positive and vice versa, using the tangential difference map from the Atlas corneal topographer. RESULTS: After overnight CRT lens wear, the central cornea flattened and the mid-periphery steepened (both p < 0.001). After 4 weeks of lens wear, the CFZ (+/-SE) increased from 3.41 +/- 0.09 mm on day 1 morning to 3.61 +/- 0.07 mm on day 28 morning and the diameter of the ASZ increased from 8.17 +/- 0.16 mm (day 1 morning) to 8.85 +/- 0.14 mm (day 28 morning) (both p < 0.001). From day 10 onwards, the CFZ and ASZ diameter were stable in the morning (p > or = 0.404). Throughout the day, the CFZ became smaller during the first 10 days (all p < or = 0.022), whereas the ASZ diameter remained constant (all p > or = 0.079). There were positive correlations between the CFZ or ASZ and residual refractive error, subjective vision and spherical aberration. The CFZ was also correlated with astigmatism and higher order aberrations, and the ASZ was positively correlated with coma (r = 0.726 to 0.961, all p < or = 0.042). In addition, there were negative correlations between the CFZ or ASZ and total aberration and defocus and between the ASZ and VA (r = -0.707 to -0.953, all p < or = 0.050). CONCLUSION: The TZ changed during the first 10 days. Its size was associated with VA, residual refractive error, aberrations and subjective vision. The concept of a TZ is a useful metric of visual, optical and subjective performance in CRT lens wearers.

Corneal refractive therapy with different lens materials, part 2: effect of oxygen transmissibility on corneal shape and optical characteristics.

PURPOSE: To compare the effects of two different oxygen transmissible (Dk/t) lenses on corneal shape and optical performance after one night of corneal refractive therapy (CRT(R)) for myopia. METHODS: Twenty myopic subjects were fit with Menicon Z (MZ) (Dk/t = 90.6, Paragon CRT(R) lenses) on one eye and an Equalens II (EII) CRT lens (Dk/t = 47.2) on the contralateral eye (eye randomized). Corneal topography, refractive error and aberrations were measured before lens insertion (baseline), and the following day after overnight lens wear, on lens removal and 1, 3, 6, 12 h later. Root mean square wavefront errors were measured using 4.5 mm pupils. RESULTS: Averaged over position and time, the horizontal corneal curvature was statistically different between the MZ and EII lens-wearing eyes (p = 0.011). The central cornea flattened similarly (p = 0.886) and the mid-periphery steepened in both eyes (p = 0.061) from baseline. The EII lens-wearing eyes were steeper in the mid-periphery than the MZ eyes immediately after lens removal and at the 1-h visit (p < or = 0.032). Central corneal flattening and mid-peripheral corneal steepening regressed over time (all p < 0.001) but did not recover to baseline by 12 h (all p < 0.004). Myopia was reduced equally by 0.84 +/- 0.83 D for the MZ-lens wearing eyes and 0.84 +/- 0.87 D for the EII eyes (p = 0.969). Coma increased from baseline 1.85X (0.056 +/- 0.081 microm) for the MZ-lens wearing eyes and 1.72X (0.048 +/- 0.084 microm) for the EII eyes (both p < 0.001). Spherical aberration increased from baseline 4.55X (0.101 +/- 0.077 microm) for the MZ-lens wearing eyes and 4.31X (0.085 +/- 0.076 microm) for the EII eyes (both p < 0.001), but there were no differences between the MZ and EII eyes (all p > or = 0.308). Coma and spherical aberration did not return to baseline by 12 h (both p < or = 0.007). CONCLUSIONS: After one night of CRT lens wear, changes in corneal shape were slightly different, with more mid-peripheral steepening in the EII eyes compared to the MZ eyes. Change in central corneal curvature and optical performance were similar in both eyes.

Corneal shape and optical performance after one night of corneal refractive therapy for hyperopia.

PURPOSE: To investigate the corneal shape and optical performance following one night of Corneal Refractive Therapy for hyperopia (CRTH). METHODS: Twenty subjects (spherical equivalent: -2.14 +/- 2.54 D) were fit with a Paragon CRTH lens (Dk = 100) on one eye randomly. The other eye served as the control. Aberrations, refractive error, and corneal topography at various locations along the horizontal meridian were measured at baseline prior to lens insertion, and immediately after lens removal and at 1, 3, 6, 12, and 28 hours later. Root mean square wavefront errors were measured using a 4.5 mm pupil size. RESULTS: After one night of CRTH lens wear, the central cornea steepened and paracentral region flattened in the experimental eyes (p < 0.001), whereas no significant location effect was found in the control eyes (p = 0.139). Refractive error (mean +/- SE) changed by 1.23 +/- 0.21 D (p < 0.001). The defocus increased by 0.58 +/- 0.09 microm (p < 0.001). Higher-order aberrations, coma, and spherical aberrations increased by factors of 2.69, 2.58, and 4.07, respectively (all p < 0.001). Spherical aberrations shifted from positive to negative. Astigmatism did not change over time (p = 0.771). All parameters returned to baseline by 28 hours (all p > or = 0.808). Aberrations and refractive error did not change in the control eyes (all p > or = 0.082). CONCLUSIONS.: The CRTH lens steepens the central cornea and flattens the paracentral region, which alters the ametropia by inducing a myopic shift. It appears to be effective for correcting hyperopia and also is reversible.

Validity of pachymetric measurements by manipulating the acoustic factor of Orbscan II.

PURPOSE: To assess the validity of pachymetric measurements by examining the constancy of the acoustic factor (AF) of the Orbscan II (Orbtek, Bausch & Lomb, Rochester, NY) after overnight rigid gas-permeable (RGP) contact lens wear. METHODS: Twenty participants wore CRT (Paragon Vision Sciences, Mesa, AZ) HDS 100 contact lenses on one eye and control lenses on the contralateral eye for one night while sleeping. Another 24 participants wore CRT lenses on both eyes for one night. Central corneal thickness was measured using optical coherence tomography and Orbscan II on the night before lens use, immediately after lens removal on the following morning, and 1, 3, 6, and 12 hours later. By using optical coherence tomography as a reference, the adjusted AF was calculated by using a least squares method over time. RESULTS: The adjusted AF depended on the corneal thickness in normally hydrated corneas. The adjusted AF and the percentage change of the adjusted AF varied before and after overnight lens wear. There was a strong and significant correlation between the corneal swelling and the percentage change of the adjusted AF (all r at least 0.91, P<0.05). CONCLUSIONS: The adjusted AF is a variable, not a constant. The AF is a function of the corneal thickness and its alteration with, for example, corneal swelling. The validity of the adjusted Orbscan II pachymetric measures using a single AF is untenable.

Reduction of myopia from corneal refractive therapy.

PURPOSE: : The purpose of the study was to monitor the efficacy of corneal refractive therapy (CRT) lenses to reduce myopia over a 4-week period. Refractive error, keratometry, high and low contrast acuity, and subjective vision after 28 days of using CRT contact lenses were measured. METHODS: : Twenty-three myopes wore CRT HDS lenses, Dk = 100. The Nikon autokefractor/keratometer was used to measure the refractive error and keratometric changes. Visual acuity was measured using computerized high and low contrast charts and the subjects completed visual analog scales characterizing their vision on a daily basis. Measurements were performed at baseline (before lens insertion before sleep), immediately after lens removal the next morning and at 1, 3, 7, and 14 hours after eye opening. Measurements were made on the days following 1, 4, 10, and 28 nights of lens wear. After 72 hours of no lens wear, these parameters were again measured to assess corneal recovery. RESULTS: : The pretreatment manifest refraction (mean of OD and OS +/- standard deviation [SD]) was -2.72 DS +/- 1.06 and -0.55 DC +/- 0.40. Myopic spherical equivalent refractive error (+/- SD) decreased by 1.30 DS +/- 0.53 (range 0-3 D) immediately after lens removal on day 1 and by 2.59 DS +/- 0.77 by day 28 (range 1.25-3.88 D). The cylinder remained unchanged. Uncorrected visual acuity improved by 5 lines after one night and reached 0.00 LogMAR (6/6) by day 4. Visual acuity was maintained throughout the day by day 10. The day and time effect of the spherical equivalent change and the central corneal radius of curvature were statistically significant (p < 0.01) up to day 10 and remained the same until day 28. Central (autokeratometer) Ks flattened by 1.28 D +/- 1.35 after one night and 2.33 D +/- 1.30 by day 28. The subjective vision improved significantly from day 1 to day 28 (p < 0.01) and was maintained throughout the day from day 4 to day 28 (p < 0.01). All measures did not recover completely to baseline after 72 hours of no lens wear. CONCLUSIONS: : CRT lenses significantly reduced myopia, improved visual acuity and subjective vision, and flattened central corneal curvature. Maximal effect was achieved after 10 days and was maintained for the rest of the study period.