Topical Prostaglandin Analogues Research Articles

First-year treatment costs among new initiators of topical prostaglandin analogs: pooled results

To estimate first-year treatment costs among new initiators of topical prostaglandin analogs in a managed care population. A model was developed to estimate first-year medical costs. Model inputs were based on weighted results from three previous studies. Treatment patterns were derived from a claims database analysis. Published studies were used to estimate visit-related resource use. Costs were obtained from standard sources. Across studies, 27,809 patients met study criteria, 44.2% of whom remained on their index therapy for 12 months. Adjunctive therapy was needed in 22.5%, 18.5%, and 11.9% of bimatoprost, latanoprost, and benzalkonium chloride (BAK)-free travoprost patients, respectively. Median days to initiating adjunctive therapy were 64, 67, and 127 for bimatoprost, latanoprost, and BAK-free travoprost patients. Estimated first-year medical costs were $1,945, $1,803, and $1,730 for patients initiating therapy with bimatoprost, latanoprost, and BAK-free travoprost. Findings were consistent through sensitivity analysis. A BAK-free prostaglandin analog may permit longer duration of monotherapy and be associated with lower first-year treatment costs. Use of a claims database and the selection of new initiators of prostaglandin analogs limit the ability to project findings to all glaucoma patients.

Comparative study of three prostaglandin analogues in the treatment of newly diagnosed cases of ocular hypertension, open‐angle and normal tension glaucoma

To compare the efficacy and tolerance of three prostaglandin analogues, bimatoprost, latanoprost and travoprost in patients with previously untreated open-angle glaucoma and ocular hypertension. Prospective randomized single (investigator) masked comparative clinical trial at the Taunton and Somerset NHS Hospital, Taunton, UK. Newly diagnosed, treatment naïve glaucoma/ocular hypertension patients were recruited. Patients were randomized into three groups to receive one of the three prostaglandin analogues. Intraocular pressure (IOP) was measured before starting treatment and after 2 and 6 months of treatment. The IOP reduction and the tolerance profile of each drug were compared. The data were analysed on the basis of intention to treat, using analysis of covariance comparing IOP in the three groups at 2 and 6 months, adjusting for baseline IOP. Tolerance levels were compared using Kruskal-Wallis test. Of the 122 patients, 40 patients were given bimatoprost, 42 received latanoprost and 40 had travoprost. At 2 months, there was a significant difference between the three treatment groups (P = 0.013) with bimatoprost achieving a greater reduction in IOP than the other two drops. However, at 6 months, the difference was not statistically significant (P = 0.13). There was no significant difference in the tolerance profile. All the three topical prostaglandin analogues are effective at lowering IOP, but bimatoprost was found to be most effective in the initial phase of the trial, and there was no statistically significant difference in the efficacy, among the three prostaglandin analogue eye drops after 6 months of treatment.

Two-year treatment patterns and costs in glaucoma patients initiating treatment with prostaglandin analogs

ObjectiveTo determine treatment patterns and costs over a two-year period among new initiators of topical prostaglandin analogs in a managed care population by retrospective cohort analysis of an insurance claims database.MethodsPatients who initiated therapy with a prostaglandin analog between September 2006 and March 2007 were identified. The use of monotherapy and adjunctive therapies were compared by index prostaglandin. Days to initiation of adjunctive therapy and rates of glaucoma surgical procedures were also calculated. Medical costs (antiglaucoma medications and ophthalmic visits) over the two-year period were estimated.ResultsThe analysis identified 5018 patients with at least one prostaglandin analog prescription (bimatoprost, n = 747; latanoprost, n = 1651; benzalkonium chloride (BAK)-free travoprost, n = 203). The majority (51%–54%) had repeat prescriptions. Among those with repeat prescriptions, 52% were female (not significant) and mean age was 64 years (P < 0.01). Rates of adjunctive therapy use varied across groups (bimatoprost 51%, latanoprost 37%, and BAK- free travoprost 35%, P < 0.0001). Median and mean days to initiation of adjunctive therapy were 83 and 140 for bimatoprost, 101 and 181 for latanoprost, and 113 and 221 for BAK- free travoprost. Two-year medical costs were $3147, $2843, and $2557 for patients initiating treatment with bimatoprost, latanoprost, and BAK-free travoprost, respectively. Use of glaucoma surgical procedures across the treatment groups was similar over the two-year period.ConclusionsOver a two-year period, the rate and time to initiation of adjunctive therapy use, as well as medical costs, varied between index prostaglandins. However, the rate of glaucoma surgical interventions did not vary significantly across index medications.

A Meta-analysis of Topical Prostaglandin Analogs in the Treatment of Chronic Angle-closure Glaucoma

To evaluate the intraocular pressure (IOP)-lowering efficacy of prostaglandin analogs topical medications in patients with chronic angle-closure glaucoma (CACG). Pertinent publications were identified through systematic searches of PubMed, EMBASE, KoreaMed, Chinese Biomedicine Database, and the Cochrane-Controlled Trials Register. Randomized clinical trials involving CACG patients treated with latanoprost, bimatoprost, or travoprost monotherapy were selected. Methodologic quality was assessed by a Delphi list with additions and scored out of a maximum of 18. The outcome measures were absolute and relative reduction in IOP from baseline, for diurnal curve, peak, and trough. The pooled effects were calculated using 2-step DerSimonian and Laird estimate method of the random effects model. Nine randomized clinical trials enrolling a total of 1,090 patients were included in the meta-analysis. Quality scores of included studies were generally high, a mean of 14.9 (range, 12-18). The difference in absolute IOP reduction between prostaglandin analogs and timolol varied from 0.4 to 1.6 mm Hg at diurnal curve, 0.9 to 2.3 mm Hg at peak, and 1.3 to 2.4 mm Hg at trough. Relative IOP reduction were diurnal curve, 31% (95% confidence interval, 27% to 34%), peak, 34% (31% to 37%), and trough 31% (28% to 35%) for latanoprost; diurnal curve, 26% (21% to 30%), peak, 28% (24% to 32%), and trough 27% (23% to 30%) for bimatoprost; diurnal curve, 28% (20% to 36%), peak, 32% (31% to 34%), and trough 31% (29% to 33%) for travoprost; and diurnal curve, 23% (19% to 27%), peak, 24% (20% to 29%), and trough 21% (19% to 24%) for timolol. Latanoprost, travoprost, and bimatoprost provide significant IOP-lowering efficacy in eyes with CACG; and the 3 prostaglandin analogs are associated with at least as effective as timolol.

First-year treatment costs among new initiators of topical prostaglandin analogs

To estimate first-year costs among new initiators of topical prostaglandin analogs in a managed care population. We developed a model to estimate first-year direct medical costs. We derived treatment patterns from a claims database analysis. Published studies were used to estimate visit-related resource use. Costs were obtained from standard sources. The database analysis identified 9,063 patients meeting study criteria, 41% (n = 3,672) of whom remained on their initial prostaglandin therapy for 12 months after initiation. Adjunctive intraocular pressure lowering therapy was needed in 20.7%, 16.5%, 13.9%, and 8.9% of bimatoprost, latanoprost, travoprost, and BAK-free travoprost patients, respectively. Median numbers of days to the first prescription filled for adjunctive therapy (if required) were 69.5, 67.0, 123.0, and 158.5 for patients initiating on bimatoprost, latanoprost, travoprost, and BAK-free travoprost. Total estimated first-year costs were $1,457, $1,360, $1,278, and $1,307 for patients initiating therapy with bimatoprost, latanoprost, travoprost, and BAK-free travoprost. Findings were consistent through sensitivity analysis. A BAK-free prostaglandin analog may permit longer duration of monotherapy and be associated with lower first-year direct medical costs. Use of a claims database and the selection of new initiators of prostaglandin analogs limit projecting findings to all glaucoma patients.

Brinzolamide/timolol fixed combination: a new ocular suspension for the treatment of open-angle glaucoma and ocular hypertension

For the treatment of open-angle glaucoma, the most frequent cause of irreversible visual loss, fixed combinations of different topical intraocular pressure (IOP) lowering molecules have gained an important role in recent years. The use of fixed combinations reduces the number of daily instillations, which promotes adherence to the prescribed medication and diminishes the exposition of the ocular surface to preservatives. The fixed combination of brinzolamide and timolol was recently approved by the European Medicines Agency (EMEA) and is now available in several countries in Europe. It contains two molecules widely used to treat glaucoma: timolol 0.5% (5 mg/ml) and brinzolamide 1% (10 mg/ml) in ophthalmic suspension formulation. This fixed combination is approved for twice-daily instillation to reduce elevated IOP in open-angle glaucoma and ocular hypertension. The brinzolamide/timolol fixed combination provides an approximately 30 – 33% IOP reduction from the untreated baseline IOP of 25 – 27 mmHg; thus, it is more potent than either of its ingredients alone. It is similarly effective but better tolerated than the dorzolamide/timolol fixed combination, which consists of molecules from the same pharmacological classes. The brinzolamide/timolol fixed combination can be used by itself as a separate therapy, but owing to the additivity of its ingredients to IOP-lowering drugs belonging to other classes, it may also be administered adjunctive to other IOP-reducing molecules, most importantly topical prostaglandin analogues. The ocular and systemic tolerance of the brinzolamide/ timolol fixed combination was reported favorable in Phase III studies, but no long-term clinical experience with this preparation is available at present.

The Impact of Ocular Adverse Effects in Patients Treated With Topical Prostaglandin Analogs: Changes in Prescription Patterns and Patient Persistence

To document patient/physician perceptions of adverse effects and their relationship to medication changes among patients prescribed prostaglandin analogs. Medical/pharmacy claims (private U.S. health network) identified patients filling initial topical ocular hypotensive prescriptions from 2001 to 2004; 300 open-angle glaucoma patients prescribed a prostaglandin analog and 103 ophthalmologists were selected by algorithm for telephone interviews. Medical charts for 225/300 interviewed and 75 non-interviewed patients were abstracted. Medication patterns were assessed in pharmacy claims data. Frequency of adverse effects noted by physicians and associations with medication change decisions were examined in charted data. Patients' experiences with adverse effects were compiled from surveys. In patients treated with latanoprost (N = 4,071), bimatoprost (N = 1,199), or travoprost (N = 1,001), continuous refill of medication through 1 year was seen in 11%, 9%, and 5% of patients, respectively (P = 0.0001; retrospective pharmacy claims). Adverse effects were the second most common reasons noted by physicians for switching medications after lack of efficacy (19% vs. 43%, respectively). Adverse effects were noted in 65% of patient charts. Hyperemia was the most common adverse effect occurring with at least one other adverse effect in 48% of patients with the condition. Ocular adverse effects, particularly hyperemia, negatively affect patient continuation with therapy and switching.

Brinzolamide/timolol fixed combination for open-angle glaucoma and ocular hypertension

The brinzolamide/timolol fixed combination contains brinzolamide 1% and timolol maleate 0.5% in ophthalmic suspension produced for twice-daily application to reduce elevated intraocular pressure in open-angle glaucoma and ocular hypertension. This fixed combination was recently approved by the European Medicines Agency, in December 2008. The brimzolamide/timolol fixed combination provides an approximately 30–33% intraocular pressure reduction from the untreated baseline of 25–27 mmHg, thus is more potent than any of its ingredients alone and is similarly effective but better tolerated than the dorzolamide/timolol fixed combination, which consists of molecules from the same drug classes. The fixed combination of brinzolamide and timolol can be used as a separate therapy, but due to the additivity of its ingredients to drugs belonging to other classes, it may also be administered in combination with other intraocular pressure-lowering molecules, most importantly topical prostaglandin analogues.

Bêta-bloquants ou prostaglandines: quel est le meilleur choix ?

The predominant place of topical beta-blockers as first-line, initial treatment for glaucoma and ocular hypertension is currently challenged with the availability of topical prostaglandin analogues. We present and discuss available data and arguments to permit to the ophthalmologist the better choice, individually tailored to a given patient, between these two therapeutic classes.

Immunohistochemical Expression of HLA-DR in the Conjunctiva of Patients Under Topical Prostaglandin Analogs Treatment

Subclinical inflammation may be observed in patients using topical antiglaucomatous drugs. The objective of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of an immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides, and prepared for immunohistochemical analysis. Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression of HLA-DR in the conjunctiva (mild). After 1 month on prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was found (P=0.27). The use of prostaglandin analogs eye drops provokes a subclinical inflammatory reaction, observed by HLA-DR expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.

First-year treatment patterns among new initiators of topical prostaglandin analogs

ABSTRACTObjective: To evaluate treatment patterns and costs among new initiators of topical prostaglandin analogs in a managed-care population.Research design and methods: Annual costs were modeled using multiple inputs. A retrospective cohort design was used to identify treatment patterns for pharmacotherapy. The study population was identified from pharmacy claims for patients who met study inclusion criteria (patients initiating prostaglandin analog monotherapy). Published studies were used to estimate visit-related resource use and costs were obtained from published and standard sources.Results: In the cohort analysis, a total of 12 202 patients met study criteria: 2275 received bimatoprost, 7347 received latanoprost and 2580 received travoprost (1808 used the original formulation and 772 used the newer preservative formulation). Of patients meeting study criteria, 50% stopped all glaucoma therapy, 6% switched from their initial prostaglandin therapy, and the remaining 44% stayed on their initial prostaglandin for 1 year. Of patients remaining on prostaglandin analog monotherapy for 1 year, 22.7% of bimatoprost patients, 19.8% of latanoprost patients and 17.9% of travoprost patients (19.7% for the original formulation and 13.7% for the new formulation) required adjunctive therapy. Of those requiring adjunctive therapy, the median number of days until starting adjunctive therapy was 53 days for bimatoprost patients, 63 days for latanoprost patients and 83 days for travoprost patients (70.5 days for the original formulation and 109 days for the new formulation). The resources used at each visit were estimated at $424 for an initial visit and $70 for follow-up visits. Estimated first-year costs were $1294, $1199, and $1186 for patients initiating therapy with bimatoprost, latanoprost, and travoprost, respectively. Estimated travoprost costs were higher for the original formulation ($1203) than for the new formulation ($1160). Sensitivity analyses suggested that the cost estimates are robust to changes in costs and use of adjunctive therapies.Limitations: The use of a claims database without compliance data or clinical outcomes and the selection of new initiators of topical prostaglandin analogs limits the findings and does not allow projecting outcomes to all glaucoma patients.Conclusions: Use of adjunctive therapy in glaucoma is an important driver of glaucoma management costs. Based on the results of this study, it is possible that longer duration of monotherapy with prostaglandin analogs may be associated with lower annual costs. Further study should be conducted to validate these findings.

Arachnoid cyst causing an optic neuropathy in neurofibromatosis 1

A 9-year-old girl with neurofibromatosis type 1 (NF1) (Fig. 1A) and a 1-year history of controlled left unilateral juvenile glaucoma, related to congenital ectropion uveae, presented with a rapid, unexplained, painless visual loss in the left eye. Eight months after the onset of visual loss, best corrected visual acuity was 20/20 in the right and 20/200 in the left eye. A relative afferent pupillary defect was observed in the left eye. Right eye examination was normal. There was a left minimal proptosis and a mild congenital ptosis. Slit-lamp examination disclosed ectropion uveae (Fig. 1B) and fundoscopy showed a glaucomatous cupped optic disc with a normally coloured neuro–retinal rim (Fig. 1C, D). Ishihara colour vision and eye motility were normal. Intraocular pressure was 14/14 mmHg on topical prostaglandin analogue treatment. Automated visual fields disclosed an unexplained left central scotoma, in addition to glaucoma-related arcuate defects (Fig. 1E, F). Cerebral and orbital magnetic resonance imaging (MRI) revealed a lesion surrounding the left intracranial portion of the optic nerve, extending into the posterior part of the optic canal (Fig. 1G).The lesion was isointense to cerebrospinal fluid (CSF) on T1- and T2-weighted images without enhancement after gadolinium injection, and an arachnoid cyst was suspected. The patient underwent decompression surgery with removal of thin, lobulated cysts around the chiasm and optic nerve. Vision did not recover postoperatively. Histopathological examination by routine paraffin technique and light microscopy demonstrated cyst walls composed of a collagen-rich, fibrillar tissue, surrounding spaces partially lined by an epithelium-like cell layer (Fig. 1H). A few psammoma bodies were found (Fig. 1I). Prussian blue stain depicted large areas of previous spontaneous bleedings within the lesion (Fig. 1J). Immunohistochemistry demonstrated that the cells of the walls reacted with vimentin antibodies (clone 3B4,), but the epithelium-like cells did not (Fig. 1H). All cells were negative for cytokeratins, (clone AE1/AE3 + 8/18, detecting cytokeratins no.: 1, 4, 5, 7, 8, 10, 13, 14, 18 and 19), glial fibrillar acidic protein (polyclonal antibody) and S-100 protein (polyclonal antibody). In summary, the tissue morphology indicated thickened dura mater and leptomeninges with a few meningothelial cells, consistent with an arachnoid cyst. (A) 9-year-old girl with neurofibromatosis type 1, showing typical café-au-lait skin pigmentations. (B) Congenital ectropion uveae of the left iris. (C) Normal right optic disc. (D) Left cupped optic disc. (E) Left visual field disclosing a paracentral scotoma in addition to glaucoma-related arcuate defects. (F) Normal right visual field (Octopus©) shown for comparison. (G) T2-weighted coronal MRI scan disclosing an arachnoid cyst surrounding the left optic nerve (asterisk). (H) Micrograph of the arachnoid cyst. The cyst wall consists of fibrillar material lined by a few epithelial-like cells. (Haematoxylin and eosin stain [H&E]; original magnification × 100.) (I) Cyst wall in higher magnification. A psammoma body is seen in purple. (H&E; original magnification × 250.) (J) Part of cyst wall. The blue areas indicate iron deposition from previous bleedings. (Prussian blue stain; original magnification × 50). Optic neuropathies are common findings in NF1 and are usually related to gliomas. Our patient had stable juvenile glaucoma caused by congenital ectropion uveae, a neural-crest-derived anterior segment dysgenesis syndrome which can be associated with NF1 (Trovó-Marqui et al. 2004). The occurrence of unexplained central visual loss, despite controlled glaucoma, prompted neuroimaging, which disclosed an intracranial arachnoid cyst extending into the optic canal, possibly precipitating the central visual loss by compression. Radiologically, orbital arachnoid cysts may mimic gliomas because the high water content of gliomatous tissue produces MRI signals identical to those of CSF (Brodsky 1993; Akor et al. 2003). In our case the lack of contrast enhancement supported the arachnoid cyst diagnosis (Cincu et al. 2007), but did not rule out the glioma. Arachnoid cysts are intracranial, space-occupying lesions of unknown pathogenesis. They are typically stable in size over time and mass symptoms are exceedingly rare (Cincu et al. 2007). Symptomatic cyst expansion can, among other causes, be related to intracystic haemorrhage (Cincu et al. 2007) and histopathology in the present case indicated previous bleeding in the cyst wall. Benign distension of normal fibrovascular tissue surrounding the visual pathways has been reported as a possible cause of compressive optic neuropathies (Akor et al. 2003). Although, as in our case, vision may not improve after surgery, biopsy for diagnosis and decompression may be warranted in atypical cases. In conclusion, in NF1, an intracranial arachnoid cyst can precipitate visual loss in a glaucomatous optic nerve, related to ectropion uveae. Glaucoma does not cause reduced central vision before the end stage of the disease, whereas central visual loss can be the presenting feature of a compressive optic neuropathy (Akor et al. 2003; Claes et al. 2006). Early detection by neuroimaging is prompted when unexplained, central visual loss occurs in glaucoma.

Topical prostaglandin analogues do not affect selective laser trabeculoplasty outcomes

To investigate the effect of topical prostaglandin analogue use on the efficacy of selective laser trabeculoplasty (SLT) intraocular pressure (IOP) lowering in patients with open-angle glaucoma. This retrospective study included 123 consecutive patients who underwent 180 degrees SLT for the first time. Eyes were grouped into those that received prostaglandin analogues before and after SLT (n=74) and those that did not (n=49). The main outcome measure was IOP lowering after SLT. Success was defined as > or =20% reduction in IOP without further glaucoma intervention. There was no significant difference in IOP lowering at 6 months post-laser between the prostaglandin and non-prostaglandin groups (3.9+/-4.8 vs 4.6+/-3.6 mm Hg, P=0.43). Long-term SLT success rates were also not significantly different between the treatment groups (Kaplan-Meier survival analysis, P=0.68). IOP lowering at 6 months was similar in eyes that received no glaucoma medications, monotherapy with or without a prostaglandin analogue, or combination therapy with or without prostaglandin analogues (P=0.81). Logistic regression analysis showed that various patient characteristics including age, sex, type of glaucoma, previous glaucoma surgery, and other glaucoma risk factors did not predict a successful SLT outcome. However, higher pre-operative IOP was found to predict SLT success (odds ratio=1.12, 95% CI=1.02-1.24, P=0.02). The IOP lowering efficacy of SLT is not influenced by the use of topical prostaglandin analogues.

Update on the Mechanism of Action of Topical Prostaglandins for Intraocular Pressure Reduction

A decade has passed since the first topical prostaglandin analog was prescribed to reduce intraocular pressure (IOP) for the treatment of glaucoma. Now four prostaglandin analogs are available for clinical use around the world and more are in development. The three most efficacious of these drugs are latanoprost, travoprost, and bimatoprost, and their effects on IOP and aqueous humor dynamics are similar. A consistent finding is a substantial increase in uveoscleral outflow and a less consistent finding is an increase in trabecular outflow facility. Aqueous flow appears to be slightly stimulated as well. Prostaglandin receptors and their associated mRNAs have been located in the trabecular meshwork, ciliary muscle, and sclera, providing evidence that endogenous prostaglandins have a functional role in aqueous humor drainage. Earlier evidence found that topical PG analogs release endogenous prostaglandins. One well-studied mechanism for the enhancement of outflow by prostaglandins is the regulation of matrix metalloproteinases and remodeling of extracellular matrix. Other proposed mechanisms include widening of the connective tissue-filled spaces and changes in the shape of cells. All of these mechanisms alter the permeability of tissues of the outflow pathways leading to changes in outflow resistance and/or outflow rates. This review summarizes recent (since 2000) animal and clinical studies of the effects of topical prostaglandin analogs on aqueous humor dynamics and recent cellular and molecular studies designed to clarify the outflow effects.

Side Effects Associated with Prostaglandin Analog Therapy

Topical prostaglandin analogs, which have become first-line therapy in the medical management of glaucoma, have an excellent safety profile with regard to systemic side effects, but are associated with several ocular side effects. Some of these are common, with no apparent serious consequences other than cosmetic, whereas others are much less common but represent potentially sight-threatening side effects. The former group includes conjunctival hyperemia, elongation and darkening of eyelashes, induced iris darkening, and periocular skin pigmentation. The latter group of side effects, which are relatively rare and lack definitive causal relationship to prostaglandin analog therapy, includes iris cysts, cystoid macular edema, anterior uveitis, and reactivation of herpes simplex keratitis. Most of the literature regarding side effects associated with prostaglandin analogs involves the use of latanoprost, probably because it was the first to be studied. There is no evidence, however, aside from less conjunctival hyperemia with latanoprost, that the commercially available prostaglandin analogs differ significantly with regard to side effects.

Uveal effusion induced by topical travoprost in a patient with Sturge-Weber-Krabbe syndrome

To report a case of uveal effusion with subtotal exudative retinal detachment induced by topical administration of travoprost. A 20-year-old woman with a medical history of right-sided Sturge-Weber-Krabbe syndrome and bilateral aphakia secondary to congenital cataract extraction was referred to our department for retinal detachment associated with uveal effusion of the right eye. The ocular manifestations of Sturge-Weber-Krabbe syndrome in her right eye were glaucoma and diffuse choroidal hemangioma. Antiglaucomatous medications using topical travoprost 0.004%/timolol 0.5% (fixed combination) had been begun 1 week before. An adverse effect of travoprost was suspected and the drug was discontinued. Three weeks later, a fundus examination showed total disappearance of the uveal effusion. Interaction of the effects of topical prostaglandin analogs (blood-aqueous barrier disruption, enhancement of uveoscleral outflow) with both the diffuse choroidal hemangioma and the elevated episcleral venous pressure may lead to uveal effusion in Sturge-Weber-Krabbe syndrome. In spite of their efficiency, prostaglandin F2 analogs (latanoprost, travoprost and bimatoprost) should be used with caution in Sturge-Weber-Krabbe syndrome and particularly in cases of proved diffuse choroidal hemangioma.

Discrepancy between Results and Abstract Conclusions in Industry- vs Nonindustry-funded Studies Comparing Topical Prostaglandins

To investigate the relationship between industry- vs nonindustry-funded publications comparing the efficacy of topical prostaglandin analogs by evaluating the correspondence between the statistical significance of the publication's main outcome measure and its abstract conclusions. Retrospective, observational cohort study. English publications comparing the ocular hypotensive efficacy between any or all of latanoprost, travoprost, and bimatoprost were searched from the MEDLINE database. Each article was reviewed by three independent observers and was evaluated for source of funding, study quality, statistically significant main outcome measure, correspondence between results of main outcome measure and abstract conclusion, number of intraocular pressure outcomes compared, and journal impact factor. Funding was determined by published disclosure or, in cases of no documented disclosure, the corresponding author was contacted directly to confirm industry funding. Discrepancies were resolved by consensus. The main outcome measure was correspondence between abstract conclusion and reported statistical significance of the publications' main outcome measure. Thirty-nine publications were included, of which 29 were industry funded and 10 were nonindustry funded. The published abstract conclusion was not consistent with the results of the main outcome measure in 18 (62%) of 29 of the industry-funded studies compared with zero (0%) of 10 of the nonindustry-funded studies (P = .0006). Twenty-six (90%) of the industry-funded studies had proindustry abstract conclusions. Twenty-four percent of the industry-funded publications had a statistically significant main outcome measure; however, 90% of the industry-funded studies had proindustry abstract conclusions. Both readers and reviewers should scrutinize publications carefully to ensure that data support the authors' conclusions.

Graft failure: III. Glaucoma escalation after penetrating keratoplasty

Glaucoma after penetrating keratoplasty is a frequently observed post-operative complication and is a risk factor for graft failure. Penetrating keratoplasty performed for aphakic and pseudophakic bullous keratopathy and inflammatory conditions are more likely to cause postoperative glaucoma compared with keratoconus and Fuchs' endothelial dystrophy. The intraocular pressure elevation may occur immediately after surgery or in the early to late postoperative period. Early postoperative causes of glaucoma include pre-existing glaucoma, retained viscoelastic, hyphema, inflammation, pupillary block, aqueous misdirection, or suprachoroidal hemorrhage. Late causes include pre-existing glaucoma, angle-closure glaucoma, ghost cell glaucoma, suprachoroidal hemorrhage, and steroid-induced glaucoma. Determining the cause of IOP elevation can help guide therapeutic intervention. Treatments for refractory glaucoma include topical anti-glaucoma medications such as beta-adrenergic blockers. Topical carbonic anhydrase inhibitors, miotic agents, adrenergic agonists, and prostaglandin analogs should be used with caution in the post-keratoplasty patient, because of the possibility of corneal decompensation, cystoid macular edema, or persistent inflammation. Various glaucoma surgical treatments have reported success in post-keratoplasty glaucoma. Trabeculectomy with mitomycin C can be successful in controlling IOP without the corneal toxicity noted with 5-fluorouracil. Glaucoma drainage devices have successfully controlled intraocular pressure in postkeratoplasty glaucoma; this is, however, associated with increased risk of graft failure. Placement of the tube through the pars plana may improve graft success compared with implantation within the anterior chamber. In addition, cyclophotocoagulation remains a useful procedure for eyes that have refractory glaucoma despite multiple surgical interventions.

Changes in Central Corneal Thickness over Time: The Ocular Hypertension Treatment Study

To describe how much change, if any, occurs between central corneal thickness (CCT) measurements performed an average of 3.8 years apart in participants in the Ocular Hypertension Treatment Study (OHTS) and to identify clinical and demographic factors that are associated with changes in CCT, including baseline intraocular pressure, duration and class of ocular hypotensive medication, medical history, and systemic medication. Secondary analysis of data from a randomized clinical trial. Ocular Hypertension Treatment Study participants. Participants who had undergone incisional intraocular or keratorefractive surgery between CCT measurements were excluded. The first CCT measurements were performed starting in 1999, and the second measurements were performed starting in 2002. Measurements were performed by OHTS certified technicians using an ultrasonic pachymeter under a standardized protocol. Central corneal thickness measurement (micrometers). First and second CCT measurements were available from 73% (1191) of the 1636 OHTS participants randomized. Central corneal thickness decreased a mean rate of -0.74+/-3.5 microm/year between the first and second CCT measurements. The mean medication exposure between first and second CCT measurements in participants originally randomized to observation (n = 595) was 1.1+/-1.6 years, versus 5.0+/-2.7 years in participants originally randomized to medication (n = 596). Central corneal thickness decreased by a mean of 1.0+/-3.4 microm/year among participants originally randomized to observation, compared with 0.5+/-3.5 microm/year among participants originally randomized to medication (P<0.0001). Subgroup analyses suggest that participants treated only with topical prostaglandin analogues (PGAs) between the two CCT measurements had a greater rate of decrease per year than participants treated only with topical beta-blockers. The rate of CCT decrease over 3.8 years is comparable to the cross-sectional age differences reported in the OHTS at the first measurement (0.6 microm/year) and comparable to other cross-sectional studies. Use of topical PGAs may be associated with a slightly higher rate of thinning. The modest age- and drug-related rates of thinning observed are unlikely to influence tonometry or clinical decision-making substantially in most clinical situations.

Morpho-Functional Follow-Up of the Optic Nerve in Treated Ocular Hypertension: Disc Morphometry and Steady-State Pattern Electroretinogram

Purpose: To examine longitudinally optic disc structure and inner retinal function in treated ocular hypertension (OHT). Materials and Methods: A morphometric (Heidelberg Retina Tomograph, HRT) and functional (steady-state pattern electroretinogram, PERG) evaluation of 27 OHT patients treated with topical beta-blockers and/or prostaglandin analogues and prospectively followed over a 24 ± 6 month period. Results: Compared with baseline, mean final PERG amplitude tended to increase (p < 0.01), while HRT was stable. Individual PERG amplitude increase was large (≥ 100%) in some patients (5/27), and unexplained by clinical parameters at baseline. Conclusions: In treated OHT, functional responses may improve while disc structure remains stable. The findings suggest that OHT-associated inner retinal dysfunction is at least in part reversible with therapeutic intraocular pressure control.