Activated forms of vascular endo-thelial growth factor and platelet-derived growth factor receptors, previously not known to exist in the vitreous, have been found to correlate with response to anti-VEGF therapy in wet age-related macular degeneration, according to researchers in
While examining whether phosphorylated VEGF receptors released into the vitreous reflect the ongoing retinal and choroidal signal pathway activity in wet AMD, the authors of the study took vitreous samples obtained im-mediately prior to anti-VEGF injection from 11 patients with choroidal neovascularization and analyzed them using reverse-phase microarrays. Two patients had samples collected at the time of injection and one month later. Samples from five patients were collected prior to vitrectomy for macular hole, epiretinal membrane or retinal detachment.
Phosphorylated forms of VEGF receptor (VEGFR Y996 and Y1175), PDGF receptor beta (PDGFR beta Y716 and Y751) and c-KIT (Y703) were present in the vitreous. A significant difference in PDGFR beta Y751 (p<0.002), VEGFR Y996 (p<0.04), and VEGFR Y1175 (p<0.006), but not c-KIT Y703 (p<0.05) or PDGFR beta Y716 (p<0.96), was noted for the responders to treatment (n=5) compared with nonresponders (n=6) and controls (n=5).
The authors conclude that vitreous levels of activated receptors constitute a new class of biomarkers and suggest that these findings could provide a foundation for developing individualized treatment and finding new therapeutic targets.
(Arch Ophthalmol 2009;127:613-21)
Davuluri G, Espina V, Petricoin EF 3rd, et al.
Studies Assess Combination Glaucoma Drugs
Two recent studies looked at different aspects of fixed-combination glaucoma drugs.
The first reported that the fixed-combination brimonidine 0.2%/timolol 0.5% (Combigan) provided the same or greater intraocular pressure-lowering capabilities when compared with fixed-combination dorzolamide 2%/timolol 0.5% (Cosopt), though brimonidine/timolol was shown to offer more ocular comfort. The authors of the study evaluated the two fixed-combination treatments when used as monotherapy or as adjunctive therapy to a prostaglandin analog in patients with glaucoma or ocular hypertension.
The results came from pooled data analysis of two randomized, investigator-masked, three-month, parallel-group studies with identical protocols (10 sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who needed lower IOP received topical brimonidine/timolol b.i.d. or dorzolamide/timolol b.i.d. as monotherapy (n=101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost or travoprost) (n=79). IOP served as the main outcome measure, being examined at 10 a.m. (peak effect) at baseline and at months one and three. Tolerability and comfort were evaluated using a patient questionnaire.
Results showed that there were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years.
There were also no statistically significant differences between groups in baseline IOP.
At month three, the mean reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (standard deviation: 4.2) mmHg (32.3 percent) with brimonidine/timolol versus 6.7 (5.0) mmHg (26.1 percent) with dorzolamide/timolol (p=0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3 percent) with brimonidine/timolol versus 5.2 (3.7) mmHg (23.5 percent) with dorzolamide/timolol (p=0.213). Pati-ents on brimonidine/timolol reported less burning (p<0.001), stinging (p<
0.001) and unusual taste (p<0.001) than patients on dorzolamide/timolol. Authors suggested that additional studies will be needed to compare the efficacy and tolerability of brimon-idine/timolol and dorzolamide/timolol during long-term treatment.
In the second report, the fixed-combination treatment brinzolamide 1%/
timolol 0.5% (Azarga) suspension provided statistically significant and clinically relevant intraocular pressure-lowering efficacy that was noninferior to dorzolamide 2%/timolol 0.5% solution. The one-year, multicenter, randomized, double-masked, active-controlled, parallel-group trial of the two fixed-combination treatments compared their IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension who required a change in therapy due to elevated IOP while receiving IOP-lowering medication.
To compare the treatments, IOP assessments were taken at 8 a.m. and 10 a.m. at week two and months three and nine, and at 8 a.m., 10 a.m. and 4 p.m. at months six and 12. Primary efficacy was a noninferiority comparison of mean IOP at each six-month time point. Of the 437 patients enrolled, 220 dosed brinzolamide/timolol whereas 217 dosed dorzolamide/timolol twice daily. Brinzolamide/timolol produced IOP-lowering efficacy comparable to dorzolamide/timolol, with the upper 95 percent confidence limits for the differences between groups within +1.5 mmHg at all assessment times, including the month six primary efficacy time points, establishing noninferiority. Differences in means numerically favored brinzolamide/timolol at nine of 12 study visits. The IOP reductions ranged from 7.2 to 9.2 mmHg for brinzolamide/timolol and from 7.4 to 8.9 mmHg for dorzolamide/timolol.
Although a similar overall safety profile was observed between the two treatment groups, brinzolamide/timolol showed significantly less ocular irritation (2.7 percent vs. 10.6 percent; p=0.0009) than dorzolamide/timolol. Additionally, brinzolamide/timolol afforded an ocular comfort advantage compared to dorzolamide/timolol.
(Curr Med Res Opin 2009. [Epub ahead of print])
Nixon DR, Yan DB, Chartrand JP, et al.
(J Glaucoma 2009;18:293-300)
Manni G, Denis P, Chew P, et al.
Haze More Likely in Younger LASIK-treated Eyes
Treating myopia with an ult-ra-thin femtosecond laser LASIK procedure could lead to interface haze, particularly in younger eyes, say Amer-ican and Brazilian researchers.
Their prospective case series evaluated 199 consecutive eyes that underwent femtosecond laser LASIK with an excimer laser. Treated eyes were divided into two groups according to desired flap thickness: 90 µm (106 eyes) and 100 to 110 µm (93 eyes). Cycloplegic refraction, spherical equivalent, uncorrected visual acuity, best spectacle-corrected visual acuity, depth of ablation, central corneal thickness, flap thickness (using optical coherence tomography), Scheimpflug images and light scattering were assessed in all eyes that developed haze postoperatively.
The study's authors found haze in 32 eyes that were treated for moderate to high myopia (spherical equivalent, -6.23 ±1.67 D; depth of ablation 94.6 ±22.9 µm) at three months postoperatively, however, ultra-thin IntraLASIK flaps (<90 µm) and younger age were both strongly associated with risk of postoperative haze (p=0.003 and p=0.01, resp-ectively). Spherical equivalent, depth of ablation and self-reported history of dry eyes were not independently associated with an increased risk of corneal haze. Patients who developed any degree of haze had significantly higher logarithmic value of scatter values (mean difference=0.24 units, p<0.0005) compared with those who did not develop haze.
The mean postoperative BSCVA was good in all eyes with haze (logarithm of the minimal angle of resolution was 0.05 ±0.04).
(Am J Ophthalmol 2009;147:966-72)
Rocha KM, Kagan R, Smith SD, Krueger RR.
Infection Rare in Outpatient Eyelid Surgery
Chances of infection in outpatient eyelid surgery tend to be ex-tremely low, suggest findings from a recent study. The study reviewed the reported cases of infections after all eyelid surgeries performed between January 1, 1999 and December 31, 2004 at the Phillips Eye Institute in
Results showed very little evidence of infection. The three most common procedures were ptosis repair (856 cases), blepharoplasty (540 cases) and ectropion or entropion correction (432 cases). Other procedures included lesion excision and eyelid reconstruction. Only one infection was reported (0.04 percent), which occurred following a bilateral upper eyelid ptosis repair and lower eyelid blepharoplasty.
The study theorizes that the low rate of infection could be due to the rich vascular anatomy of the eyelid.
(Ophthal Plast Reconstr Surg 2009;25:109-10)
Lee EW, Holtebeck AC,