Anterior chamber aqueous flare is a strong predictor for proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment.

PURPOSE: To investigate preoperative aqueous flare as a predictive factor for proliferative vitreoretinopathy (PVR) redetachment in patients with rhegmatogenous retinal detachment. METHODS: Preoperatively, the aqueous flare of 116 consecutive patients with retinal detachment was measured quantitatively with a laser flare-cell meter (Kowa FM-500; Kowa Company, Ltd, Tokyo, Japan). Seventy-four healthy partner eyes and 41 eyes of healthy age-matched patients served as controls. At least 6 months after surgery, patients were reevaluated, whether surgery was performed again because of PVR redetachment. RESULTS: Eyes with retinal detachment that developed PVR redetachment later on (n = 12) had higher flare values than eyes with uncomplicated retinal detachment (n = 104) (median, 27.63 vs. 8.83 photon counts per millisecond; P < 0.0001). No eye with PVR redetachment had a flare value <10.8 photon counts per millisecond. In eyes with flare values exceeding 15 photon counts per millisecond, the odds of PVR redetachment development increases 16-fold. CONCLUSION: Our study shows that the breakdown of the blood-ocular barrier as determined by aqueous flare is a major risk factor for PVR redetachment. The laser flare-cell meter is a fast, noninvasive, and safe tool that allows predicting the PVR redetachment risk preoperatively. It provides the surgeon with an estimate to choose those patients who could benefit from intravitreal drugs to prevent PVR.

Intravitreal Corticosteroid Implantation in Diabetic Macular Edema: Updated European Consensus Guidance on Monitoring and Managing Intraocular Pressure.

Intravitreal therapy for diabetic macular edema can, in susceptible patients, increase intraocular pressure (IOP). As uncontrolled IOP can potentially be sight threatening, monitoring is an essential component of patient management. It can be challenging for retina specialists to ensure that monitoring is rigorous enough to detect and resolve any potential problems at the earliest opportunity without it also being overburdensome for patients who have the lowest risk of developing an IOP rise. We have developed dynamic algorithms that: (1) tailor the frequency and extent of monitoring according to individual susceptibility and current IOP and (2) assist retina specialists in deciding when they should consider a referral to a glaucoma specialist. One algorithm is for patients with a relatively low susceptibility to developing an IOP rise (those whose baseline IOP is < 22 mmHg and who do not have a history of IOP events). Depending on their first post-implantation IOP check, the algorithm classifies them as: low risk if IOP remains < 22 mmHg; medium risk if IOP is 22-25 mmHg and any rise from baseline is < 10 mmHg; or high risk if IOP is > 25 mmHg or any rise from baseline is ≥ 10 mmHg. Thereafter, the algorithm guides on the frequency and extent of monitoring required in each of these groups and, if IOP rises or falls during treatment, patients may move up or down the risk groups accordingly. A different algorithm is provided for patients who are more susceptible to developing an IOP rise (those with a baseline IOP of ≥ 22 mmHg or a prior history of an IOP event). These patients need monitoring more closely so this algorithm has only medium- or high-risk classifications. These algorithms update the previous monitoring guidance by Goñi et al. (Goñi et al. in Ophthalmol Ther 5:47-61, 2016).

Some people with diabetes have macular edema, which is a swelling of the central part of the retina (the tissue that lines the back of the eye). This swelling can threaten eyesight if untreated.Injecting a drug such as a corticosteroid into the eye can help treat the condition. Sometimes this has a side effect of increasing intraocular pressure (pressure within the eye). A small or short-lived rise in eye pressure should be no cause for concern, but it is very important to ensure the pressure is not too high for too long­because this could lead to the loss of eyesight. To prevent this happening, an eye doctor needs to check the eye pressure regularly.Some people are more susceptible to this problem­for example, people who have had any problems related to eye pressure in the past or people whose eyes already have a higher than normal pressure even before treatment. People who are most susceptible may need more types of checks and more frequent checks to ensure that any problems are found and treated quickly.We have developed flowcharts that help eye doctors decide which checks are needed and how often based on what the doctor knows about the person's eye before treatment and what they see at each check-up after treatment. They help doctors make sure that everyone has check-ups at the right time and they help doctors spot any problems early so that they can be resolved before long-lasting damage can occur.

Electronic compliance monitoring of topical treatment after ophthalmic surgery.

The success of many medical treatments is built on compliance. Electronic monitoring is the most accurate tool to quantify compliance by measuring adherence. In order to assess the efficiency of a recently introduced miniature monitoring device for eye drop application, we evaluated adherence in ophthalmic patients undergoing post-operative short-term topical treatment. This pilot study enrolled 30 outpatients (mean age 61.8 +/- 18.5 years) after cataract (n = 24) and glaucoma filtration surgery (n = 6) applying fixed-combination eye drops containing prednisolone and gentamicin five times daily for 2 weeks. Patients received eye drops in conventional bottles each equipped with a miniature monitoring device recording events of application. Two patients failed to bring back the monitoring device; therefore data collected from only 28 patients could be examined. Data showed highly variable results with a mean dose compliance of 50.2%. Dose compliance was below 25% in approximately one out of five patients. Four cataract patients, but no glaucoma patient, discontinued therapy prematurely. The observed mean dosage interval was calculated for each patient and ranged 4.6-19.7 h. Thirty percent of analysed dosage intervals exceeded 12.0 h. Different patterns of compliance behaviour-like early non-persistence, drug holiday and low treatment frequency could be identified and illustrated using electronic data. Age or gender did not significantly influence compliance rates. Our pilot study demonstrates successful electronic compliance monitoring using a technology capable of continuous data recording over weeks of treatment. The low compliance rate for a relevant part of the patients demonstrates the necessity to study and improve compliance in ophthalmology. In future, new application methods and electronic application devices may improve treatment response in eye care.

Modelling ocular pharmacokinetics of fluorescein administered as lyophilisate or conventional eye drops.

OBJECTIVE: The objective of this evaluation was to model ocular pharmacokinetics of fluorescein administered as conventional eye drops and as lyophilisate to healthy volunteers in order to assess the relative bioavailability of the lyophilisate formulation. METHODS: A total of 44 healthy subjects received equivalent doses of fluorescein as lyophilisate to one eye and as eye drops to the fellow eye in three individual studies. Fluorescein concentrations in the cornea and anterior chamber were measured by fluorophotometry. Data were analyzed by noncompartmental methods (WinNonlin software) and by compartmental population pharmacokinetic methods (NONMEM software). RESULTS: Compared to eye drops, both maximum fluorescein concentrations (C(max)) and the areas under the concentration-time curve (AUC(0-t )) values of fluorescein in the cornea and anterior chamber for lyophilisate were increased in the noncompartmental analysis: mean lyophilisate C(max) in the studies was 6.3- to 14.6-fold higher and mean AUC(0-t ) was 4.7- to 8.9-fold higher for ocular concentrations in the three studies. A three-compartment open model with first-order elimination from the anterior chamber adequately described population data. Estimated fluorescein systemic bioavailability (F) via the ocular route from lyophilisate relative to eye drops was 3.7-fold higher (95% CI 2.6-4.8). CONCLUSION: The data clearly show a considerably superior intraocular bioavailability of fluorescein when given as lyophilisate compared to conventional eye drops. There is a clear pharmacokinetic advantage of the lyophilisate preparation.

Optimization Strategies for Bruch's Membrane Opening Minimum Rim Area Calculation: Sequential versus Simultaneous Minimization.

To compare a simultaneously optimized continuous minimum rim surface parameter between Bruch's membrane opening (BMO) and the internal limiting membrane to the standard sequential minimization used for calculating the BMO minimum rim area in spectral domain optical coherence tomography (SD-OCT). In this case-control, cross-sectional study, 704 eyes of 445 participants underwent SD-OCT of the optic nerve head (ONH), visual field testing, and clinical examination. Globally and clock-hour sector-wise optimized BMO-based minimum rim area was calculated independently. Outcome parameters included BMO-globally optimized minimum rim area (BMO-gMRA) and sector-wise optimized BMO-minimum rim area (BMO-MRA). BMO area was 1.89 ± 0.05 mm2. Mean global BMO-MRA was 0.97 ± 0.34 mm2, mean global BMO-gMRA was 1.01 ± 0.36 mm2. Both parameters correlated with r = 0.995 (P < 0.001); mean difference was 0.04 mm2 (P < 0.001). In all sectors, parameters differed by 3.0-4.2%. In receiver operating characteristics, the calculated area under the curve (AUC) to differentiate glaucoma was 0.873 for BMO-MRA, compared to 0.866 for BMO-gMRA (P = 0.004). Among ONH sectors, the temporal inferior location showed the highest AUC. Optimization strategies to calculate BMO-based minimum rim area led to significantly different results. Imposing an additional adjacency constraint within calculation of BMO-MRA does not improve diagnostic power. Global and temporal inferior BMO-MRA performed best in differentiating glaucoma patients.

Intraday Repeatability of Bruch's Membrane Opening-Based Neuroretinal Rim Measurements.

Purpose: To assess possible intraday variability in Bruch's membrane opening-based (BMO) assessment of neuroretinal rim by spectral-domain optical coherence tomography (SD-OCT) of the optic nerve head (ONH) as well as to evaluate its independence from intraindividual IOP changes. Methods: In this noninterventional, prospective cohort study, 51 consecutively enrolled patients with glaucoma or ocular hypertension underwent standardized SD-OCT of the ONH and IOP assessment at two different time points with a time gap of 5 hours on the same day. Random effects models, intraclass correlation coefficients (ICC) and Bland-Altman plots were used to analyze repeatability of BMO minimum rim width (BMO-MRW) and area (BMO-MRA) and peripapillary retinal nerve fiber layer (RNFL) thickness measurements. Results: Mean BMO area was 1.86 ± 0.30 mm2. At baseline, mean BMO-MRW was 206.46 ± 0.86 µm, mean BMO-MRA was 0.89 ± 0.34 mm2, and mean RNFL thickness was 71.61 ± 0.20 µm. Within intraindividual measurements, mean difference was 2.95 µm or 1.76% for BMO-MRW, 0.02 mm2 or 2.68% for BMO-MRA, and 1.18 µm or 1.89% for RNFL thickness. Comparing time points, η2 was 0.001 (P = 0.757) for RNFL thickness, 0.043 (P = 0.01) for BMO-MRA, and 0.07 (P = 0.06) for BMO-MRW. Intraclass correlation coefficients were greater than 0.994, respectively. Variability of morphometric parameters did not correlate to intraindividual IOP fluctuations. Conclusions: Assessment of BMO-MRW by SD-OCT shows high intraday repeatability, which is comparable to the parameter RNFL thickness. Variability seems not to be driven by typical moderate intraday fluctuations of IOP. The two-dimensional parameter BMO-MRA incorporates a fairly higher intraindividual variability.

A 12-week, randomized, double-masked, multicenter study of the fixed combination of latanoprost and timolol in the evening versus the individual components.

PURPOSE: To compare the efficacy and tolerability of fixed-combination latanoprost and timolol applied in the evening with the concomitant use of the individual components. DESIGN: Twelve-week, randomized, double-masked, multicenter study. PARTICIPANTS: Five hundred seventeen randomized patients with ocular hypertension; open-angle, pigmentary, or exfoliation glaucoma; and baseline (after washout) intraocular pressure (IOP) levels between 23 and 33 mmHg. METHODS: Patients received either the fixed combination of latanoprost and timolol once daily in the evening and a placebo in the morning and evening or the unfixed combination of latanoprost once daily in the evening and timolol in the morning and evening. Study visits were at weeks 2, 6, and 12. MAIN OUTCOME MEASURES: The primary efficacy end point was mean change from baseline to week 12 in diurnal IOP (mean IOPs of 8 am, 12 pm, and 4 pm). The fixed combination was considered noninferior to the unfixed combination if the upper limit of the 95% confidence interval (CI) of the difference was <1.5 mmHg (analysis of covariance). Adverse events were recorded at each visit. RESULTS: In all, 502 patients were included in intent-to-treat analyses (fixed combination, n = 255; unfixed combination, n = 247). For the fixed- and unfixed-combination groups, mean baseline diurnal IOP levels were 25.4 mmHg and 25.2 mmHg, respectively, and mean diurnal IOP reductions were 8.7 mmHg and 9.0 mmHg (between-treatment difference, 0.3 mmHg; 95% CI, -0.1 to 0.7 mmHg; P = 0.15). Both treatments were well tolerated. CONCLUSIONS: The fixed combination of latanoprost and timolol administered once daily in the evening is not inferior to the unfixed combination of latanoprost once daily in the evening and timolol twice daily. The fixed combination provides an effective and well-tolerated alternative to multiple instillations.

Elevated Intraocular Pressure After Intravitreal Steroid Injection in Diabetic Macular Edema: Monitoring and Management.

INTRODUCTION: With the increasing use of intravitreal administration of corticosteroids in macular edema, steroid-induced intraocular pressure (IOP) rise is becoming an emergent issue. However, for patients in whom intravitreal steroids are indicated, there are no specific recommendations for IOP monitoring and management after intravitreal administration of corticosteroids. METHOD: An expert panel of European ophthalmologists reviewed evidence on corticosteroid-induced IOP elevation. The objective of the panel was to propose an algorithm based on available literature and their own experience for the monitoring and management of corticosteroid-induced IOP elevation, with a focus on diabetic patients. RESULTS: Data from trials including diabetic patients with a rise of IOP after intravitreal steroid administration indicate that IOP-lowering medical treatment is sufficient for a large majority of patients; only a small percentage underwent laser trabeculoplasty or filtering filtration surgery. A 2-step algorithm is proposed that is based on the basal value of IOP and evidence for glaucoma. The first step is a risk stratification before treatment. Patients normotensive at baseline (IOP ≤ 21 mmHg), do not require additional baseline diagnostic tests. However, patients with baseline ocular hypertension (OHT) (IOP > 21 mmHg) should undergo baseline imaging and visual field testing. The second step describes monitoring and treatment after steroid administration. During follow-up, patients developing OHT should have baseline and periodical imaging and visual field testing; IOP-lowering treatment is proposed only if IOP is >25 mmHg or if diagnostic tests suggest developing glaucoma. CONCLUSION: The management and follow-up of OHT following intravitreal corticosteroid injection is similar to that of primary OHT. If OHT develops, IOP is controlled in a large proportion of patients with standard IOP treatments. The present algorithm was developed to assist ophthalmologists with guiding principles in the management of corticosteroid-induced IOP elevation. FUNDING: Alimera Sciences Limited.

Photodynamic therapy to control fibrosis in human glaucomatous eyes after trabeculectomy: a clinical pilot study.

OBJECTIVE: To evaluate the safety, tolerability, and clinical effect on intraocular pressure (IOP) of a carboxyfluorescein ester as an adjunctive antifibrotic therapy in human glaucomatous eyes to control postoperative wound healing after trabeculectomy. METHODS: In 10 human glaucomatous eyes with high IOPs that underwent 1 to 3 previous surgical procedures for glaucoma, 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester was applied 15 minutes prior to trabeculectomy via a subconjunctival injection followed by intraoperative illumination with diffuse blue light (450-490 nm; approximately 51.9 x 10(3) candelas/m(2)) for 8 minutes. Antifibrotic efficacy was established by clinical response, postoperative IOP reduction, slitlamp examination, and filtering bleb site photographs. Success was defined as an IOP less than 21 mm Hg from baseline without the eye receiving any antiglaucomatous medication or an application of antimetabolites. RESULTS: The mean (SD) IOP on the day before surgery was 37.2 (11.2) mm Hg. The IOP was 16.6 (3.8) mm Hg in 8 successful eyes after a mean (SD) follow-up of 400.1 (38.1) days (P<.001). Two eyes showed scarring at the site of the filtering bleb within 1 month. In 1 eye with pseudoexfoliation glaucoma IOP decreased to 17 mm Hg but needed topical antiglaucomatous medication. Clinical examination revealed none of the following: blebitis, uveitis, endophthalmitis, or toxic damage of the adjacent tissues. CONCLUSIONS: We report our findings about the first 10 consecutive human glaucomatous eyes treated with a single dose of 80 microg of 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester during trabeculectomy. In contrast to chemotherapeutic agents, cellular photoablation acts only on cells having incorporated 2'7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester and having been exposed to light of an appropriate wavelength. Though safety and efficacy demand a controlled randomized study, our method seems to be an effective therapeutic approach to control postoperative fibrosis in human glaucomatous eyes with a poor surgical prognosis. Multiple factors such as dose of light, means of application, wavelength, irradiation area, total dose of the dye, and multiple dosing may be altered in the future to improve the antifibrotic effect of photodynamic therapy during surgery for glaucoma.

Combined therapy of pilocarpine or latanoprost with timolol versus latanoprost monotherapy.

Adjunctive intraocular pressure (IOP)-lowering therapy is widely used today, as one-third of all patients being treated for glaucoma need additional therapy to reach and maintain healthy IOPs. Timolol, latanoprost, and pilocarpine are three potent drugs that have been used in combination to reduce IOP. Timolol reduces the production rate of aqueous humor to achieve the IOP decrease. Latanoprost and pilocarpine both affect aqueous outflow, although by different mechanisms. The IOP efficacy of combined therapy with timolol and pilocarpine compared with timolol and latanoprost or with latanoprost alone has been investigated in three multicenter, randomized, clinical trials in Europe. This is a review of those published trials. In 2 of the 3 studies, the additional IOP lowering effect of latanoprost 0.005% administered once daily was compared with pilocarpine 2% administered 3 times daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension currently on monotherapy with timolol 0.5% twice daily. These 6-month studies found that the timolol and latanoprost combination reduced IOP more and was better tolerated with fewer side-effects than the timolol and pilocarpine combination. At 6 months, there was no evidence of long-term drift in IOP with timolol and latanoprost. This combined therapy provides an effective and safe option for lowering IOP in glaucoma patients. These results suggest that the timolol/latanoprost combination is preferable to the timolol/pilocarpine combination not only with regard to side effects but also to the magnitude of IOP reduction. Two of the 3 studies compared latanoprost monotherapy with timolol and pilocarpine combined therapy in patients with POAG, various other glaucomas, or ocular hypertension. Treatment was for 6 weeks or 6 months. In both studies, latanoprost was more effective and better tolerated than the combination of timolol and pilocarpine. These results suggest that latanoprost alone should be tried before the addition of pilocarpine to timolol therapy is considered. The convenience of daily administration of a single drop of latanoprost versus multiple drops of timolol and pilocarpine should improve patient compliance.

The ophthalmic lyophilisate carrier system (OLCS): development of a novel dosage form, freeze-drying technique, and in vitro quality control tests.

The ophthalmic lyophilisate carrier system (OLCS) is a novel dosage form for delivery of pharmacologically active ingredients or other substances improving the structure of the tear film to the eye. A drop of lyophilisate containing the drug and bulk forming water-soluble or swelling excipients is attached to a flexible hydrophobic carrier. Placebo OLCS and OLCS containing several drugs commonly used in ophthalmology were compared to conventional eye drops containing the same ingredients. A novel lyophilization procedure for the production of this dosage form is described, which allows stricter control of the freezing and drying conditions and shortens the production cycle by at least an order of magnitude. In clinical studies it was found that OLCS are easy to administer and well tolerated if the force of adhesion between lyophilisates and carrier strips and the structural firmness of the lyophilisates themselves are well controlled. These parameters are critical for convenient administration and complete delivery of the dose of active ingredients incorporated, therefore suitable in vitro tests were developed with which their values can be determined for the purpose of process validation. A study of fluorescein OLCS in humans indicated that concentration profiles in the cornea and anterior chamber are significantly higher than after administration of equal doses of the diagnostic in conventional eye drops.

Tolerability and safety of two new preservative-free tear film substitutes.

PURPOSE: The tolerability, safety, and visual comfort of two new tear film substitutes were studied in a phase I clinical study. METHODS: Two amphipathic lipids (phosphatidylcholine, cholesterol, sphingomyelin, and gangliosides) containing solutions (I and II) of well-defined stoichiometry, free of preservatives, were studied in 20 eyes of 20 healthy volunteers (age range, 26-32 years) in a randomized, double-blind, crossover study. Randomization was achieved by treating one eye of each volunteer four times daily for 7 days with composite solution I. The contralateral eye served as a control. After a washout interval of 7 days, the same eye was treated similarly four times daily with the solution II under randomizing conditions. Slit-lamp biomicroscopy, visual acuity, visual analog scales, and side effects were monitored at the beginning of the study weekly and for 3 weeks. RESULTS: The tear substitutes proved to have no influence on the visual acuity and were safe and well tolerated. No allergic reactions or any other side effects such as hyperemia, corneal disturbance, and foreign body deposits were observed in any volunteer. CONCLUSION: The biophysical properties of the amphipathic lipids comprising the two preservative-free tear film substitutes were studied in monolayer experiments. They form reversibly compressible and expandable monomolecular films at the air-water interface, a prerequisite for the mimicry of the tear film produced normally by meibomian glands. The efficacy and safety of both medications will be investigated in patients with keratoconjunctivitis sicca and dry eye syndrome in future experiments.

Measurement of adherence to brimonidine therapy for glaucoma using electronic monitoring.

PURPOSE: To assess the patient adherence and behavior with brimonidine twice daily (bid) or 3 times daily (tid) in patients used to topical glaucoma medication. PATIENTS AND METHODS: Seventy-five patients with glaucoma or ocular hypertension were enrolled in a prospective, observational cohort study. Consenting patients were randomly assigned to brimonidine bid or tid and received conventional brimonidine eye drops with attached electronic monitoring devices for 4 weeks. Patients were not explicitly informed on the compliance monitoring. RESULTS: The study was completed by 67 patients (89%). In 65 patients (97%), at least 1 dosing interval exceeded 24 hours. The mean adherence rates were better in the brimonidine bid group (72 ± 19% vs. 62 ± 16%, P=0.04), although dosing frequency was higher in the tid group (1.9 ± 0.5 vs. 1.4 ± 0.4 per day; P<0.001). On average medication coverage was 70% for the bid group and 67% for the tid group; 19 patients (28%) had a coverage rate above 75%, 42 patients (63%) 50% to 75%, and 6 (9%) below 50%. Patients with normal-tension glaucoma had lower coverage rates than patients with primary open-angle glaucoma and ocular hypertension (P<0.05). Data also showed that on average 20% of the glaucoma medication was wasted owing to inefficient drug delivery by using more than 1 drop per dosing. CONCLUSIONS: Individual adherence with brimonidine was highly variable and pharmacologically insufficient for more than two-third of the patients. Special attention should be paid to compliance of patients with normal-tension glaucoma. Our findings underline the need to improve individual adherence and drug delivery in topical glaucoma therapy.

Adherence with brimonidine in patients with glaucoma aware and not aware of electronic monitoring.

PURPOSE: To assess the impact of open versus masked adherence monitoring on adherence with topical brimonidine using two different dosing schedules. METHODS: Thirty-seven patients with glaucoma or ocular hypertension were enrolled in a prospective, observational cohort study. Patients were randomly assigned to open or masked adherence monitoring and to brimonidine twice daily (BID) or three times daily (TID). Patients received conventional brimonidine eye drops with attached electronic monitoring devices for 4 weeks with weekly intraocular pressure measurements. Adherence calculations comprised dosing intervals, adherence rate and time covered. Subgroup analysis with anova included the factors masking, regimen, diagnosis and age. RESULTS: Among 36 individually analysed patients, 12 (33%) had adherence rates above 75%, therein two (5%)>90%. The mean adherence rate in 19 patients aware of adherence measurements was 70 ± 17% for brimonidine BID and 65 ± 14% for TID, not significantly different to the rates of 17 patients not informed about adherence measurements (77 ± 6% BID, 62 ± 9% TID, p = 0.24). On average, patients with brimonidine TID achieved significantly lower adherence rates (64 ± 12%) than patients on BID (73 ± 13%, p = 0.02). Still, patients on TID applied brimonidine more often (TID 1.9 ± 0.3, BID 1.5 ± 0.1 mean applications per day). The median coverage was 70% and showed no statistically significant difference between patients on BID and TID (p = 0.36). CONCLUSION: The study findings suggest that adherence measurements are not significantly altered by open adherence monitoring, which may simplify future adherence studies. Adherence with brimonidine eye drops was insufficient for most patients. These results demonstrate the necessity to develop new strategies to improve compliance in glaucoma therapy.

Photodynamic therapy for wound-healing modulation in pterygium surgery. A clinical pilot study.

BACKGROUND: This study was performed to evaluate the safety and efficacy of photodynamic therapy with the carboxyfluorescein ester BCECF-AM as an adjunctive treatment procedure for pterygium surgery to reduce the rate of recurrence. METHODS: In this nonrandomized prospective clinical trial, 19 eyes with nasally located primary pterygium were examined. All eyes were treated with the bare sclera surgical technique. Seven eyes received in addition treatment with BCECF-AM solution and blue light. All patients were evaluated at least after 1 day, 1 week, 1 month, 3 months, and 1 year. Postoperative fibrovascular growth from the limbus of at least 1 mm was defined as recurrence. RESULTS: The intraoperative application of BCECF-AM solution did not cause anterior chamber flare or any other significant side effects. The bare sclera surgery rate of recurrence was 0% (zero of 12) after 3 months and 91% (11 of 12) after 1 year. The additional photodynamic therapy treatment had a rate of recurrence of 14.2% (one of seven) after 3 months and 71.4% (five of seven) after 1 year. CONCLUSIONS: The applied PDT technique seems to be a safe procedure but is associated with a high rate of recurrence. In conclusion, the evaluated PDT treatment procedure, at this point, should not be considered. As we found a high rate of recurrence also in the control group, the bare sclera technique is not effective, even in primary pterygia.

Interobserver variability in confocal optic nerve analysis (HRT).

BACKGROUND/AIMS: To study the observer-related variability of optic nerve head (ONH) measurements using confocal laser scanning tomography (HRT I) in a screening setting. METHODS: Six experienced glaucoma specialists independently evaluated 50 ONH topographies from 25 adults using HRT software ver. 2.01 in a masked fashion. ONH topographies were obtained from a cohort study of 882 healthy adults and additionally included one patient with glaucomatous eyes. A glaucoma-screening-like setting was intended. The mean interobserver difference was defined as the mean percentual difference between an observer's analysis and the mean of all six observers for all eyes and all observers. The interobserver range was calculated for each eye as the percentual difference between the lowest and highest measurement, with the highest measurement as denominator. Additionally, Kendall's coefficient of rank concordance was assessed for the main HRT parameters. RESULTS: Mean disc area ranged from 1.83 +/- 0.49 to 2.21 +/- 0.40 mm(2) (mean interobserver difference: 8.3%; interobserver range: 5-50%; rank concordance: 0.86). The lowest mean interobserver differences were found for mean retinal nerve fibre layer thickness (RNFLT; 6.5%), maximum cup depth (2.9%) and cup shape (6.8%). An increased interobserver range was significantly correlated to a low cup to disc area ratio (r=0.64, P<0.0001). CONCLUSIONS: The observer-dependent diagnostic variability of HRT measurements can lead to divergent diagnostic evaluation of the ONH in a screening setting. Any HRT software relying on a reference database is exposed to relevant observer-related variability of the disc area. For screening purposes, HRT measurements should be completed by other diagnostic methods to compensate for possible diagnostic uncertainty.

The influence of Latanoprost 0.005% on aqueous humor flow and outflow facility in glaucoma patients: a double-masked placebo-controlled clinical study.

BACKGROUND: Fluorophotometry and pneumotonography were performed to investigate the effect of Latanoprost 0.005% and Placebo on aqueous humor flow and total outflow facility in human glaucomatous eyes. METHODS: In a randomized double-blind clinical study patients with POAG and OHT receive either Latanoprost 0.005% or placebo once in the evening. Fluorophotometry (Fluorotron Master II, Ocumetrics) and, Pneumotonography, Mentor) was performed in 20 eyes of 10 patients (verum) and 22 eyes of 11 patients (placebo). During a 2 week wash-out period all patients received a systemic antiglaucomatous therapy (Acetazolamide) up to 3 days before baseline measurement. Patients with IOP higher than 28 mmHg at baseline were excluded. Fluorophotometry, tonography and IOP were measured at baseline after 1 and 2 weeks of treatment. Data was analysed by the Student's paired t test. RESULTS: All patients completed the protocol. The IOP significantly decreased (25%) after 1 and 2 weeks of treatment with Latanoprost(p<0.01). Fluorophotometry measurements showed no difference in flow over time in both groups. Although tonographic mean C values in both groups did not show any difference over time, the estimated total outflow facility C (Goldmann) increased significantly (p<0.05) in the verum-treated eyes after 2 weeks. A significant difference of outflow co-efficient correlated to normal pressure (P0/C) was found after 2 weeks of treatment with Latanoprost (p<0.05). CONCLUSIONS: In accordance with the literature we found a mean 25% decrease in IOP after 2 weeks of treatment with Latanoprost 0.005%. The analysis of the flow values in both groups showed no increase or decrease in aqueous humor dynamics as proved in many previous studies. The known effect of Latanoprost increase uveoscleral outflow by remodeling extracellular matrix and widening intermuscular spaces in the ciliary body may not detected by pneumotonography after 2 weeks of treatment. The significant increase in estimated total outflow facility (Goldmann formula) in latanoprost-treated eyes and the decrease of IOP took place at constant flow rates. The increase in conventional outflow facility may indicate trabecular meshwork changes, but it cannot explain the significant decrease in IOP. Furthermore, an additional effect, e.g. uveoscleral outflow, may play the major role as considered in many previous studies.

The short-term effect of latanoprost on intraocular pressure and pulsatile ocular blood flow.

PURPOSE: There is evidence that ocular blood flow plays a critical role in the clinical course of glaucoma. Any reduction in ocular blood flow due to topical antiglaucoma treatment should therefore be avoided. This study aimed to evaluate the short-term effect of local latanoprost application on ocular hemodynamics. METHODS: Intraocular pressure (IOP), ocular pulse amplitude (OPA), ocular pulse volume (OPV), systemic blood pressure, heart rate and the pulsatile component of ocular blood flow (POBF) were recorded using a pneumotonometer linked to the Langham Ocular Blood Flow System in 24 patients in a prospective, open-label study before and after 1 week of topical latanoprost application in both eyes. Twenty of the subjects had primary open-angle glaucoma and four had ocular hypertension. RESULTS: After 1 week of latanoprost treatment, IOP decreased significantly 6.2 +/- 2.9 mmHg in OD (P < 0.001) and 6.2 +/- 3.2 mmHg in OS (P < 0.001). Pulsatile OBF increased significantly by 201.2 +/- 167.4 microL/min in OD (P < 0.001) and 203.8 +/- 187.3 microL/min in OS (P < 0.001). Ocular pulse amplitude and OPV showed statistically significant increases (P < 0.05 and P < 0.001 respectively). Blood pressure and heart rate did not change significantly. CONCLUSION: Our results indicate that 1 week after latanoprost application, POBF, OPA and OPV were significantly increased in the eyes treated. More information on the perfusion of the optic nerve head is needed before the relevance of these findings to optic nerve head blood flow can be interpreted correctly.