Assessment of corneal sublayer thickness changes in glaucoma patients using optical coherence tomography and correlation of epithelial layer thinning with dry eye monitoring.

BACKGROUND: In this study, we aimed to assess the central corneal epithelial thickness (CET), central corneal stromal thickness (CST), and total central corneal thickness (CCT) thinning relationships with dry eye development monitoring and underestimated measurement of intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients treated with timolol, dorzolamide, and brimonidine. METHODS: This longitudinal cohort study included 106 patients with POAG. All patients underwent a detailed ophthalmic examination. In addition, CET, CST, and CCT were measured using anterior segment optical coherence tomography (AS-OCT). Subsequently, the cohort was divided into three groups based on the therapy administered. The Tomec group received monotherapy with benzalkonium chloride (BAK)-preserved timolol + dorzolamide fixed combination. The Alphagan group received monotherapy with purite-preserved brimonidine, and the Combigan group received monotherapy with BAK-preserved timolol + brimonidine fixed combination. RESULTS: CET, CST, and CCT did not show a statistically significant decrease in the Alphagan group (p>0.05). However, the Tomec and Combigan groups showed significantly reduced measurements, except for stromal thickness (p<0.05). Finally, a significant positive correlation was found between changes in tear break-up time (TBUT) and CET during the follow-up period (r = 0.637, p = 0.001). CONCLUSIONS: CET and CCT thinning were higher in the Tomec and Combigan groups than in the Alphagan group. Furthermore, although CCT reduction was significant in the Tomec and Combigan groups, its effect on IOP underestimation was approximately 1%. Furthermore, the positive correlation between CET and TBUT suggests that CET measurement with AS-OCT may also be useful in dry eye monitoring.

Evaluation of the anti-Acanthamoeba activity of two commercial eye drops commonly used to lower eye pressure.

Efficient treatments against Acanthamoeba Keratitis (AK), remains until the moment, as an issue to be solved due to the existence of a cyst stage which is highly resistant to most chemical and physical agents. In this study, two antiglaucoma eye drops were tested for their activity against Acanthamoeba. Moreover, this study was based on previous data which gave us evidence of a possible link between the absences of Acanthamoeba at the ocular surface in patients treated with beta blockers for high eye pressure both containing timolol as active principle. The amoebicidal activity of the tested eye drops was evaluated against four strains of Acanthamoeba using Alamar blue method. For the most active drug the cysticidal activity against A. castellanii Neff cysts and further experiments studying changes in chromatin condensation levels, in the permeability of the plasmatic membrane, the mitochondrial membrane potential and the ATP levels in the treated amoebic strains were done. Even though both eye drops were active against the different tested strains of Acanthamoeba, statistical analysis revealed that one of them (Timolol Sandoz) was the most effective one against all the tested strains presenting IC50s ranging from 0.529% ± 0.206 for the CLC 16 strain to 3.962% ± 0.150 for the type strain Acanthamoeba castellanii Neff. Timolol Sandoz 0.50% seems to induce amoebic cell death by damaging the amoebae at the mitochondrial level. Considering its effect, Timolol Sandoz 0.50% could be used in the case of contact lens wearers and patients with glaucoma.

Effects of 0.2% brimonidine and 0.2% brimonidine-0.5% timolol on intraocular pressure and pupil size in normal equine eyes.

BACKGROUND: Brimonidine is an α2 -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or glaucomatous equine eyes. OBJECTIVES: To evaluate the efficacy and safety of brimonidine in lowering intraocular pressure (IOP), alone and in conjunction with timolol, as a treatment for equine glaucoma by comparing IOP in normal equine eyes treated with brimonidine and brimonidine-timolol, respectively, with IOP in control eyes. STUDY DESIGN: A balanced crossover design with 16 horses receiving one of two treatments, brimonidine and brimonidine-timolol, during each of two 10-day study phases, was used. Four horses were randomly assigned to each of four combinations of treated eye (right or left) and drug order within the two 10-day study phases (brimonidine first or brimonidine-timolol first). METHODS: Pupil size and conjunctival hyperaemia were assessed twice per day and IOP was measured three times per day using rebound tonometry in both eyes of 16 normal horses throughout two 10-day study periods (brimonidine and brimonidine-timolol) separated by an 18-day washout period. One eye of each horse was treated with brimonidine or brimonidine-timolol and the opposite eye was treated with balanced salt solution (BSS). RESULTS: There were no adverse effects and no significant changes in pupil size in normal equine eyes treated with brimonidine or brimonidine-timolol. Average IOP in normal equine eyes treated with brimonidine (25.6 mmHg) was statistically higher than in eyes treated with brimonidine-timolol (24.6 mmHg) or BSS (24.5 mmHg). However, IOP differences were of ≤1 mmHg and thus not clinically important. MAIN LIMITATIONS: Horses with normal eyes may not be as sensitive to the IOP-lowering effects of treatment as horses with glaucoma. CONCLUSIONS: Brimonidine and brimonidine-timolol are well tolerated in normal horses but do not decrease IOP.

Pharmacologic Management of Pressure-Induced Stromal Keratopathy after LASIK.

PURPOSE: To emphasize the importance of anticipation of pressure-induced stromal keratopathy (PISK) in eyes with a previous history of LASIK. CASE REPORT: A 40-year-old man developed LASIK-related pressure-induced stromal keratopathy after uneventful phacoemulsification (Phaco) and intraocular lens (IOL) implantation in his left eye. With immediate discontinuation of the steroid drops and initiation of antiglaucoma medication, his visual acuity, interface edema, and haze improved rapidly. One year later, during Phaco with IOL implantation in his other eye, with anticipation of a similar LASIK-related pressure-induced stromal keratopathy, a very brief course of soft steroid therapy was given together with antiglaucoma medication. Intraocular pressure elevation was avoided, and no interface edema or haze was observed. CONCLUSIONS: This case illustrates that the risk for LASIK-related pressure-induced stromal keratopathy may be reduced with appropriate precautions.

[Current therapeutic possibilities for uveal ocular hypertension].

OBJECTIVE: to evaluate the efficacy of combination therapy with three antiglaucoma agents (dorzolamide + brimonidine/timolol) for uveal ocular hypertension. MATERIAL AND METHODS: The study enrolled 20 patients with anterior uveitis complicated by intraocular pressure (IOP) elevation. Besides standard anti-inflammatory agents, the treatment included IOP-lowering instillations, namely dorzolamide 2% 3 times daily and timolol 0.5% 2 times daily. Those patients whose IOP remained uncompensated were then switched to a three-drug regimen: dorzolamide 2% 3 times daily and a fixed combination of brimonidine 0.2%, an aLPHA2-receptor agonist, and timolol 0.5%, a 3-blocker, 2 times daily (Combigan, Allergan). IOP was measured with Maklakov tonometer three times during the day before the treatment and then three times daily while performing the two- or three-drug combination therapy. RESULTS: The mean initial IOP was 34.57 +/- 0.09 mmHg with daily fluctuations of 5.2 +/- 0.08 mmHg. After starting the unfixed combination therapy (dorzolamide + timolol) the mean IOP decreased by 7.86 +/- 0.07 mmHg. Switching to the three-drug therapy (dorzolamide+ brimonidine/timolol) enabled an additional decrease in IOP by 5.43 +/- 0.06 mmHg. Thus, with the new regimen the total decrease in IOP averaged 13.29 +/- 0.09 mmHg with daily fluctuations of 2.5?0.06 mmHg, which ensured that the target IOP was achieved in all patients. All the drugs were well-tolerated. CONCLUSION: Combination therapy with three antiglaucoma agents in the form of two medications--dorzolamide 2% and brimonidine/timolol fixed combination (Combigan)--is shown to be effective in uveal ocular hypertension patients.

Efficacy of topical brimonidine-timolol for haemangioma of infancy and perils of off-label prescribing.

We report three patients with superficial haemangiomas treated topically with Combigan ophthalmic solution (brimonidine 0.2%-timolol 0.5%), a combination selective α-2-adrenergic agonist and non-selective ß-blocker Food and Drug Administration-approved for use in glaucoma. Topical brimonidine 0.2%-timolol 0.5% therapy improved the appearance of haemangiomas in all the cases. Two patients did not experience any adverse effects. One patient had hypothermic episodes which were initially thought to be because of brimonidine 0.2%-timolol 0.5% therapy. However, an episode occurred a few weeks after discontinuation and brimonidine 0.2%-timolol 0.5% therapy was ruled out as a cause. Despite the benefit, off-label use of brimonidine 0.2%-timolol 0.5% therapy served as a pitfall in the evaluation of an unusual constellation of worrisome symptoms. In conclusion, brimonidine 0.2%-timolol 0.5% therapy is a promising alternative in the topical treatment of haemangiomas. It may have synergistic effects and increased efficacy by targeting haemangiomas via two mechanisms (α-agonism and ß-inhibition), but the risk of unforeseen adverse effects must always be considered when prescribing off-label treatment, especially in infants.

Combining the isoabsorptive point in the ratio spectrum and the smart ratio difference methods for a single step determination of compounds with overlapped spectra.

A new method significantly advantageous over the conventional spectrophotometric methods regarding simplicity, minimal data processing and applicability was developed. The new method is based on the fact that isoabsorptive points whenever present in an absorption spectrum will be retained even after division by a one component as a divisor in the ratio spectrum, in addition to a smart modification of the conventional ratio derivative and ratio subtraction methods. This modified method though simpler, enabled wider range of applications. The proposed method was applied for the analysis of brimonidine and timolol in laboratory prepared mixtures with mean percentage recoveries 100.64 ± 1.10 and 100.96 ± 1.16, respectively, and in their pharmaceutical formulation with mean percentage recoveries 100.88 ± 0.34 and 100.84 ± 0.72, respectively. The suggested method was validated according to USP guidelines and can be applied for routine analysis in quality control laboratories.

[Effect on ocular blood flow of Combigan® versus placebo in patients with ocular hypertension]. / Efecto de Combigan(®) versus placebo en el flujo sanguíneo ocular en pacientes hipertensos oculares.

PURPOSE: This study was undertaken to compare the ocular haemodynamic effects of Combigan(®) versus placebo in patients with ocular hypertension (OHT). METHODS: Thirty patients with OHT were included in a controlled, randomised, double blind study in two parallel groups; 15 were randomised to receive Combigan(®) and 15 to receive placebo for a period of 3 months. At baseline and at 3 months retrobulbar blood flowmeasurements of the ophthalmic artery (OA) and central retinal artery (CRA) were taken using colour Doppler imaging(CDI) ultrasound, concurrently with intraocular pressure (IOP). RESULTS: Combigan(®) significantly reduced IOP after 3 months of treatment (P = 0.001), whereas placebo showed no significant change in IOP. The baseline haemodynamic parameters were similar between treatment and placebo groups. Patients treated with Combigan® showed a statistically significant decrease in CRA resistive index (P = 0.007). CONCLUSIONS: Patients treated for 3 months with Combigan(®) showed a significant decrease of CRA resistive index that could be explained by the decrease in IOP.

[The latest developments in glaucoma therapy using fixed combination products]. / Actualitati în tratamentul glaucomului cu combinatii fixe medicamentoase.

Modern fixed-combination products simplify medication dose regimen without sacrificing their effectiveness.Potential benefits of the therapy with fixed-combination products are enhanced tolerability increased convenience,better compliance,cost and time economy and removal of the wash out effect. Regarding intraocular pressure lowering effect, fixed-combination agents are superior to monotherapy with the two medication components, with the exception of Duotrav that is not superior to travoprost action.Fixed-combination products are noninferior to concomitant administration of the two components of medication (nonfixed-combination agents) relative to their ocular hypotensive efficacy with the exception of Ganfort that is however inferior to concurrent administration of both the bimatoprost and timolol.