Deepening Of The Upper Eyelid Sulcus Research Articles

Recovery from Upper Eyelid Sulcus Deepening Following Switch from Prostaglandin Analogues to EP2 Receptor Agonist

Purpose: To report a case of recovery from deepening of the upper eyelid sulcus after switching from prostaglandin FP receptor agonists to an EP2 receptor agonist.Case summary: A 65-year-old male patient with suspicion of glaucoma presented for detailed examinations. At the initial visit, his best-corrected visual acuity was 1.0 in both eyes, and the intraocular pressure (IOP) was 14/14 mmHg. Examination revealed no specific findings in the anterior segment, mild early cataracts bilaterally, and moderate glaucomatous changes. Therefore, bimatoprost/timolol fixed-combination eye drops were administered in both eyes. After 1 month, the IOP was 11/11 mmHg and no evidence of glaucoma progression was found. After 10 months, the IOP was 17/18 mmHg and there was deepening of the upper eyelid sulcus bilaterally. Consequently, bimatoprost/timolol fixed combination eye drops were switched to omidenepag isopropyl. Within 2 months of the switch, the deepening of the upper eyelid sulcus recovered completely and the IOP was 14/13 mmHg.Conclusions: Patients with prostaglandin-associated periorbitopathy should be switched to non-prostaglandin drugs or EP2 receptor agonists. Our patient exhibited complete recovery of the upper eyelid sulcus deepening after switching to an EP2 agonist.

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves' Ophthalmopathy.

Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

Influence of 0.002% Omidenepag Isopropyl on Intraocular Pressure and the Cornea in Normal Tension Glaucoma.

Although Omidenepag isopropyl drops elicited stable intraocular pressure reductions in NTG patients, transient changes in refraction and corneal endothelial cells, significant increase of central corneal thickness, and corneal erosion should be considered. To analyze the efficacy and safety of 0.002% omidenepag Isopropyl (OMDI) eye drops in patients with normal tension glaucoma (NTG). Medical records for 62 eyes treated with OMDI for ≥6 months were analyzed. Intraocular pressure (IOP), refraction, keratometry, central corneal thickness (CCT), endothelial cell count, coefficient of variation of endothelial cell area (CV), corneal erosion, and central retinal thickness were compared at baseline and 1, 3, and 6 months. IOP significantly decreased from 13.4±3.8 to 11.9±3.0, 11.7±2.9, and 12.2±3.3mmHg at each follow-up ( P <0.001). Endothelial cell count did not change, but CV transiently increased from 12.6 to 17.0 at 1 month, CCT increased from 531.5 to 538.4μm, myopia changed from -1.5 to -1.9 D, and keratometry changed from 44.5 to 44.7 D. CV, myopia, and keratometry recovered to baseline at 6 months; however, CCT remained high. Significant corneal erosion was observed at 6 months. Central retinal thickness changes were not observed. There were improvements in prostaglandin-associated skin pigmentation (86.7%), eyelash elongation (40.0%), and deepening of the upper eyelid sulcus and ptosis (~30%) at 3 months after exchange to OMDI. Adverse reactions were corneal erosion (27.4%), corneal thickening (21.0%), conjunctival hyperemia (11.3%), photophobia (5.7%), blurred vision (5.7%), and anterior chamber cells (4.8%). OMDI eye drops elicited significant and stable IOP reductions after 6 months in NTG patients with low IOP. However, transient myopic and corneal endothelial cell changes, development of corneal thickening, and corneal erosion should be considered when using OMDI.

Prostaglandin-Associated Periorbitopathy Symptom Alleviation After Switching Prostaglandin F Receptor Agonist to EP2 Receptor Agonist in Patients with Glaucoma.

Purpose: Prostaglandin-associated periorbitopathy in patients with glaucoma is reportedly not caused by EP2 agonist, but it has been a cosmetic problem with prostaglandin F receptor (FP) agonists. In this study, patients with prostaglandin-associated periorbitopathy on FP agonists were switched to EP2 agonist and changes were investigated. Methods: Patients complaining of prostaglandin-associated periorbitopathy were included. The FP agonist was switched to EP2 agonist (omidenepag isopropyl), and patients were followed up for 7 months. Frontal photographs were taken at every visit, and objective changes in deepening of the upper eyelid sulcus were assessed by three observers. Subjective questionnaires (self-awareness of deepening of the upper eyelid sulcus, eyelid/peri-eyelid skin pigmentation, eyelash elongation, and conjunctival hyperemia) were acquired at the start and the endpoint. Factors associated with the change of prostaglandin-associated periorbitopathy were investigated using logistic regression analysis. Results: Included were 23 eyes of 23 patients (17 women; 60.6 years). At 7 months, objective deepening of the upper eyelid sulcus improved by 76%. The subjective questionnaires showed that deepening of the upper eyelid sulcus improved in 95%, eyelid/peri-eyelid skin pigmentation in 76%. The less extent of myopia was a significant factor in the eyes with improved eyelid/peri-eyelid skin pigmentation. After switching, no change in intraocular pressure or visual acuity was observed (P ≥ 0.22). Conclusion: Switching to omidenepag isopropyl increased patient satisfaction and might be the first step to lightening deepening of the upper eyelid sulcus and eyelid/peri-eyelid skin pigmentation. It was suggested that pigmentation may be more easily improved in nonmyopic eyes.

Association between personality traits and experience of adverse periocular reactions to topical prostaglandin analogues

BackgroundAesthetically unappealing adverse periocular reactions to prostaglandin (PG) eye-drops are a major challenge in glaucoma treatment. This study analysed the personality traits of patients with glaucoma based on a five-factor...

Periocular Adverse Reactions to Omidenepag Isopropyl

To investigate the periocular adverse reactions to omidenepag isopropyl (OMDI). Nonrandomized comparative clinical study. We enrolled 100 patients (100 eyes) with primary open-angle glaucoma or ocular hypertension who received initial treatment with OMDI or tafluprost in only 1 eye for ≥6 months. Photographs of the eyelids were taken on the day of the participants' visit after ≥6 months of prescription. Subsequently, 3 ophthalmologists individually determined the occurrence of eyelid pigmentation, eyelash growth, and deepening of the upper eyelid sulcus (DUES). Additionally, a questionnaire on the subjective symptoms was administered. Multivariate analysis of baseline data was performed to investigate the factors involved in adverse reactions. The mean duration of drug administration was 10.2 ± 3.8 and 10.8 ± 4.1 months in the OMDI and tafluprost groups, respectively. The frequencies of eyelid pigmentation, eyelash growth, and DUES were 0.0%, 0.0%, and 2.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 4.0%, 32.0%, and 12.0%. The only significant difference was that the OMDI group showed fewer patients with eyelash growth than in the tafluprost group (P < .0001). In the questionnaire, the subjective symptoms of eyelid pigmentation, eyelash growth, and DUES were 8.0%, 2.0%, and 4.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 12.0%, 40.0%, and 4.0%, respectively. Multivariate analysis revealed a correlation between the type of drug administered and these adverse reactions (R=0.38, P=.005). The frequencies of periocular adverse reactions to OMDI, ranging from 0% to 2.0%, were lower than those to tafluprost.

Recovery of deepening of the upper eyelid sulcus after switching from prostaglandin FP receptor agonists to EP2 receptor agonist: a 3-month prospective analysis.

To examine the effect of switching from a prostanoid FP receptor agonists to EP2 receptor agonist (omidenepag isopropyl) on the deepening of the upper eyelid sulcus (DUES) and intraocular pressure (IOP) in Japanese glaucoma patients over 3months post treatment. Prospective observational study. Patients with glaucoma who received FP receptor agonists treatment and had complained of DUES-related reduction in quality of life were included. Their FP receptor agonists was switched to omidenepag isopropyl without a drug holiday. At baseline and 1 and 3months post-switch, photographs were taken and the changes in DUES were assessed by three independent observers. IOP and adverse events were also assessed. The study included 23 eyes of 23 patients (6 men, 17 women; average age, 60.6years). After switching, DUES improved in 12 eyes at 1month and in 16 eyes at 3months; eyes in the remaining patients showed no worsening of the condition. The mean IOP before switching was 15.3 ± 3.3mmHg (95% confidence interval 13.9-16.7mmHg). Following the switch, the mean IOP values were 15.6 ± 3.3mmHg (14.1-17.0mmHg) at 1month and 15.5 ± 3.3mmHg (14.1-16.9mmHg) at 3months (P = 1.0 at 1month, P = 1.0 at 3months; both adjusted by Bonferroni correction). No adverse effects were observed. Omidenepag isopropyl improved DUES while maintaining IOP in over 70% of Japanese patients with glaucoma who exhibited DUES caused by FP receptor agonists; the improvement was observed within 3months after switching from FP receptor agonists.

Prostaglandin F2\u03b1 agonists induced enhancement in collagen1 expression is involved in the pathogenesis of the deepening of upper eyelid sulcus

Previous our study reported that three-dimension (3D) cultures of human orbital fibroblasts (HOFs) replicated the etiology of deepening of the upper eyelid sulcus (DUES) caused by prostaglandin F2α analogues (PGF2α-ags). To examine this further, the effects of PGF2α-ags on HOFs were characterized by (1) lipid staining (2D; two-dimension, 3D), (2) comparison of the 3D organoid sizes of preadipocytes (DIF−) or adipocytes (DIF+) that had been treated with various concentrations of several PGF2α-ags, (3) physical stiffness (3D), and (4) the mRNA expression of adipogenic related genes, extracellular matrix (ECM), tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) (3D). PGF2α-ags caused a dramatic down-sizing of the 3D DIF+ organoids and this reduction was concentration dependent. The effects caused by PGF2α-ags were also observed in 3D preadipocytes. Micro-squeezer analysis clearly indicated that PGF2α-ags induced an increase in their physical solidity. The size of each organoid under several conditions was inversely correlated with the mRNA expression profile of collagen1 (COL1), TIMP2, and MMP2 and 9. These findings indicate that PGF2α-ags affect the expression of COL1, TIMP2, and MMP2 and 9 which, in turn, modulate the 3D ECM network within the organoids, thus resulting in their downsizing.

Corneal topographic changes after blepharoptosis surgery in patients with deepening of the upper eyelid sulcus.

We analyzed the corneal topography before and after blepharoptosis surgery and examined whether there was a difference in the corneal topographic changes with and without deepening of the upper eyelid sulcus (DUES). Retrospective study. A total of 23 eyes of 23 patients (6 men and 17 women) were enrolled in this study. The patients were divided into two groups according to the presence or absence of DUES, and their clinical characteristics were compared. There were no significant differences between the DUES (n = 9) and non-DUES (n = 14) groups in any of the parameters examined before blepharoptosis surgery, including age, best-corrected visual acuity (BCVA), margin reflex distance-1 (MRD-1), spherical equivalent, average keratometry (AveK), cylindrical power (CYL), corneal higher order aberrations (HOAs) and central corneal thickness (CCT). In the non-DUES group, BCVA, spherical equivalent, AveK, CYL, and CCT were not significantly different between before and after surgery. On the other hand, in the DUES group, BCVA, spherical equivalent, and CCT were not significantly different before or after surgery, however, AveK, CYL and HOAs showed significant decreases after surgery. In addition, related to the post-surgical changes in CYL, the DUES group had a higher rate of reduced CYL. It is expected that in eyes with DUES blepharoptosis surgery can reduce AveK, CYL and HOAs in association with postoperative corneal flattening, and that will contribute to improvements in visual function.

Association of Deepening of the Upper Eyelid Sulcus with the Incidence of Blepharoptosis after Glaucoma Filtration Surgery

ABSTRACT Purpose: To examine the clinical characteristics of patients who developed blepharoptosis after filtering surgery. Study Design: A retrospective, observational study. Methods: 96 eyes in 79 patients who underwent glaucoma filtration surgery were included in this study. These patients were followed up for more than one year after filtration surgery. The clinical characteristics were compared between two groups: a group that developed blepharoptosis during the follow-up, and a group that did not develop blepharoptosis. Results: Of the 96 eyes in 79 patients who underwent filtration surgery, 12 eyes (12.5%) developed blepharoptosis and underwent blepharoptosis surgery. There were no significant differences between the two groups in any of the following: age, sex, presence or absence of simultaneous cataract surgery, differences in surgical procedures (conventional trabeculectomy or trabeculectomy with an Ex-Press mini-glaucoma shunt device), number of needlings after filtration surgery, glaucoma type and number of anti-glaucomatous drugs before filtration surgery. Deepening of the upper eyelid sulcus (DUES) was found in 6 of the 12 eyes (50.0%) of the blepharoptosis group and 9 of the 84 eyes (10.7%) of the non-blepharoptosis group, and a significant difference was observed (p < .01). When blepharoptosis patients without DUES after filtration surgery were used as a reference, there was a significant difference in odds ratios between these patients and blepharoptosis patients with DUES (OR: 8.56; 95% CI: 2.30–32.21; p < .01). Conclusion: The development of blepharoptosis after filtration surgery is an important issue, and the presence of DUES may be a risk factor for postoperative blepharoptosis after glaucoma filtration surgery.

Omidenepag, a non-prostanoid EP2 receptor agonist, induces enlargement of the 3D organoid of 3T3-L1 cells

2D and 3D cultures of 3T3-L1 cells were employed in a study of the effects of Omidenepag (OMD), interacting with a non-prostanoid EP2 receptor, on adipogenesis. Upon adipogenesis, the effects on lipid staining, the mRNA expression of adipogenesis-related genes (Pparγ, CEBPa, Ap2, and Glut4) and the extracellular matrix (ECM) including collagen type 1, 4 and 6, and fibronectin, and the size and physical property of 3D organoids were compared between groups that had been treated with EP2 agonists (butaprost and OMD) and PGF2α. Upon adipogenesis, these significantly suppressed lipid staining and the mRNA expression of related genes. EP2 agonists and PGF2α influenced the mRNA expression of ECM in different manners, and these effects were also different between 2 and 3D cultures. Examining the physical properties by a microsqueezer indicated that the solidity of the 3D organoids became significantly lowered upon adipogenesis and these effects were not affected by EP2 agonists. In contrast, 3D organoid stiffness was markedly enhanced by the presence of PGF2α. These observations indicate that EP2 agonists affect the adipogenesis of 3T3-L1 cells in different manners, as compared to PGF2α, suggesting that OMD may not induce PGF2α related orbital fat atrophy, called the deepening of the upper eyelid sulcus (DUES).

One-Year Follow-Up Study of Changes in Prostaglandin-Associated Periorbital Syndrome After Switch From Conventional Prostaglandin F2alfa to Omidenepag Isopropyl.

BackgroundCosmetic problems induced by conventional prostaglandin F2α (PGF2α) analogs are common. We prospectively evaluated the improvement of patients with prostaglandin-associated periorbital syndrome (PAPS) for whom the treatment regimen was switched from conventional PGF2α analogs to a new selective prostaglandin-EP2 agonist (i.e., omidenepag isopropyl).MethodsWe finally evaluated 12 patients with follow-up for one year who changed the therapy from conventional PGF2α drugs to omidenepag isopropyl. Digital facial images of the patients were captured prior to the initiation of therapy with omidenepag isopropyl and after approximately three, six, and 12 months. Three independent observers judged the recovery according to the five signs of PAPS - deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation - by comparing images at baseline and each month.ResultsThe mean age of patients (eight females; four males) was 61 years. The original PGF2α drugs were bimatoprost (N = 7), latanoprost (N = 3), travoprost (N = 1), and tafluprost (N = 1). The mean duration of treatment with PGF2α was 61 months. PAPS signs were evaluated in 11 patients after three months and in all 12 patients after six and 12 months. After three, six, and 12 months, DUES improved in five, six, and six patients, respectively; flattening of the lower eyelid bags improved in two, two, and three patients, respectively; upper eyelid ptosis improved in zero, one, and two patients, respectively; ciliary hypertrichosis improved in zero, one, and zero patients, respectively; and eyelid pigmentation improved in one, five, and three patients, respectively. Recovery of DUES was the most observed sign at ≤50%, whereas the recovery of ciliary hypertrichosis was the least sign at ≤8% at 12 months. All patients with improved DUES at one year had been receiving bimatoprost or travoprost.ConclusionsSome PAPS signs improved after the administration of omidenepag isopropyl for one year. Our findings are useful for patients suffering from cosmetic problems induced by conventional PGF2α analogs.

Effectiveness of Blepharoptosis Surgery in Patients With Deepening of the Upper Eyelid Sulcus.

The purpose of this retrospective study was to evaluate the effectiveness of blepharoptosis surgery in patients with deepening of the upper eyelid sulcus (DUES). This case series included 10 consecutive patients (19 eyes) with DUES associated with use of a prostaglandin analog for glaucoma. Patients who had used bimatoprost and developed DUES were changed to an alternative prostaglandin analog and observed for ≥3 months. If there was no improvement, they underwent levator resection for blepharoptosis and were followed up for ≥6 months postoperatively. Improvement in margin reflex distance-1 and surgical complications was evaluated. After discontinuation of bimatoprost in 3 cases (6 eyes), mild subjective and objective improvement in DUES was seen in 2 cases (4 eyes) but without improvement in blepharoptosis. The prostaglandin analog used before surgery was travoprost in 4 eyes (21.0%), tafluprost in 7 eyes (36.9%; including 4 eyes switched from bimatoprost), and latanoprost in 8 eyes (42.1%; including 2 eyes switched from bimatoprost). The mean margin reflex distance-1 value was 1.11 ± 0.96 mm before surgery and 3.72 ± 0.81 mm at the final postoperative follow-up; the difference was significant (P = 3.32 × -10). There were no intraoperative or postoperative complications. Levator resection is a useful and safe procedure for blepharoptosis with DUES.

Prostaglandin F2α Agonists Negatively Modulate the Size of 3D Organoids from Primary Human Orbital Fibroblasts.

PurposeTo elucidate the molecular etiology of deepening of the upper eyelid sulcus (DUES) induced by prostaglandin (PG) analogs, a three-dimensional (3D) tissue culture system was employed using human orbital fibroblasts (HOFs).MethodsDuring adipogenesis, changes in HOF 3D organoid sizes, as well as their lipids stained by BODIPY and expression of the extracellular matrix (ECM) by immunolabeling and/or quantitative PCR, were studied in the presence or absence of either 100-nM bimatoprost acid or 100-nM prostaglandin F2α.ResultsThe size of the 3D organoids increased remarkably during adipogenesis, but such increases were significantly inhibited by the presence of PG analogs. Staining intensities by BODIPY and mRNA expression of peroxisome proliferator-activated receptor gamma were significantly increased upon adipogenesis but were not influenced by the presence of PG analogs. Unique changes in ECM expression observed with or without adipogenic differentiation were significantly modified by the presence of PG analogs.ConclusionsOur present study indicates that PG analogs have the potential to modulate the ECM network within HOF 3D organoids. Thus, a 3D tissue culture system may be a suitable strategy for understanding the disease etiology of DUES.

Prostaglandin F2\u03b1 agonist-induced suppression of 3T3-L1 cell adipogenesis affects spatial formation of extra-cellular matrix

To establish a deepening of the upper eyelid sulcus (DUES) model that can be induced by prostaglandin (PG) analogues, a three-dimension (3D) tissue culture was employed. Upon adipogenesis of the 3T3-L1 organoid, the effects of either Bimatoprost acid (BIM-A), or PGF2α were examined. During the adipogenesis, organoid size, lipid staining by BODIPY and expression of the extracellular matrix (ECM) by immunocytochemistry and/or quantitative PCR were employed. The size of the organoid increased remarkably during the adipogenesis, while such increases were significantly inhibited by the presence of PGF2α or BIM-A. BODIPY positive lipid-laden cells significantly increased during the adipogenesis, while in contrast they were greatly suppressed by the presence of PGF2α. Characteristic and spatial changes in ECM expressions observed upon adipogenesis were greatly modified by the presence of PGs. Our present study using a 3D tissue culture may be a suitable strategy toward understanding disease etiology of DUES.

Changes in Prostaglandin-associated Periorbital Syndrome After Switch from Conventional Prostaglandin F2α Treatment to Omidenepag Isopropyl in 11 Consecutive Patients.

We evaluated the recovery of patients with PAPS for whom the treatment regimen switched from conventional prostaglandin F2α analogues to a new selective prostaglandin-EP2 agonist: omidenepag isopropyl. From November 2018 to July 2019, we prospectively evaluated 11 patients who had been using conventional PGF2α drugs. Digital photographs of the patients were taken before the start of omidenepag isopropyl therapy and ~3 and 6 months after. Three independent observers used the photographs to judged recovery according to the 5 signs of PAPS: deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation. The mean age of patients was 61, and 7 patients were female. The original PGF2α drugs were bimatoprost, latanoprost, travoprost, and tafluprost. The mean duration of PGF2α treatment was 65 months. PAPS signs were evaluated in 10 patients after 3 months and in all 11 patients after 6 months: After 3 and 6 months, DUES improved in 3 and 3 patients, respectively; flattening of the lower eyelid bags improved in 1 and 2 patients, respectively; upper eyelid ptosis did not improve in any patients; ciliary hypertrichosis improved in 0 and 2 patients, respectively; and eyelid pigmentation improved in 2 and 8 patients, respectively. The 3 patients who showed improvement in DUES at 6 months had all previously used bimatoprost. Some PAPS signs improved after patients started taking omidenepag isopropyl. Our findings will be useful for patients taking antiglaucoma eye drops.

Pretarsal skin height changes in children receiving topical prostaglandin analogue therapy for primary congenital glaucoma

To compare pretarsal skin height (PTSH), as proxy indicator of deepening of the upper eyelid sulcus, in children with primary congenital glaucoma (PCG) treated with topical prostaglandin analogues (PGAs) with PTSH in healthy children (control group 1) and children with PCG but not using PGAs (control group 2). We recruited children with PCG who had been using PGAs for at least 6months (PCG/PGA group). PTSH in all participants was measured using ImageJ software from photographs taken in a standardized manner. The PTSH was compared for the PCG group and both control groups. A total of 34 children with PCG and 41 controls (31 in group 1; 10 in group 2) were included. The difference in PTSH between children in the PCG/PGA group and both control groups was statistically significant (mean difference, ≥1.7mm [P<0.01]). The PTSH was significantly greater in children with PCG using PGAs compared to children with PCG not using PGAs and healthy children. Children and their parents should be counseled about lid abnormalities prior to commencing treatment with PGAs.

Effects of pre-surgical administration of prostaglandin analogs on the outcome of trabeculectomy.

For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0.001) lower in the bimatoprost group (31.3%) than in the latanoprost (83.2%), tafluprost (45.5%), or travoprost groups (65.6%). Deepening of the upper eyelid sulcus (DUES) was observed before trabeculectomy in 18 of 74 eyes (24.3%) treated with bimatoprost (9 eyes; 50.0%), latanoprost (3 eyes; 16.7%), tafluprost (1 eye; 5.5%) and travoprost (5 eyes; 27.8%). The proportion of patients with no recurrent IOP elevation up to 24 months post-trabeculectomy was significantly (P < 0.0001) lower in the DUES(+) group (34.7%) than in the DUES(-) group (74.3%). Multivariate stepwise logistic regression analysis, with no recurrent IOP elevation used as dependent variable, and bimatoprost, latanoprost, travoprost, tafluprost, β-blocker, carbonic anhydrase inhibitor, brimonidine, gender, age, preoperative IOP, mean deviation, duration of PG analog use before surgery, and the number of ophthalmic solutions used as independent variables, identified only bimatoprost as a significant independent factor (P = 0.0368). Thus, the outcome of trabeculectomy varied depending on the PG analog used preoperatively, and bimatoprost use was associated with a high risk of recurrent IOP elevation up to 2 years post-trabeculectomy. This may indicate that the incidence of DUES differed with the PG analog used. Patients with glaucoma who are treated with bimatoprost should be monitored for DUES, and when these patients undergo trabeculectomy, the postoperative course of IOP should be followed carefully.

Prostaglandin-associated periorbitopathy in latanoprost users.

PurposeWe investigated the incidence of prostaglandin-associated periorbitopathy (PAP) in subjects with glaucoma treated with latanoprost ophthalmic solution.Subjects and methodsOne eye and the forehead in 22 subjects were evaluated. All patients had used latanoprost for more than 1 year (range, 12 to 45 months; mean, 26.0 months) and were prostaglandin F2α analogue treatment-naïve. Digital photographs of the subjects obtained before latanoprost therapy and at the last examination were compared retrospectively. Four signs of PAP (deepening of the upper eyelid sulcus (DUES), upper eyelid ptosis, flattening of the lower eyelid bags, and inferior scleral show) and supplemental side effects around the eyelids (eyelash growth, poliosis, and eyelid pigmentation) were judged to be negative or positive by three independent observers. If the observers unanimously rated a sign as positive, the result was defined as positive.ResultsTwelve subjects (54.5%) had no apparent signs. Three subjects were judged to have DUES (13.6%), and two subjects each were judged to have flattening of the lower eyelid bags and eyelid pigmentation (9.0%). The other signs were judged as positive in only one subject each, respectively (4.5%). A univariate logistic regression analysis showed no significant associations between any of the signs and age, sex, or the duration of therapy.ConclusionLatanoprost induced DUES, upper eyelid ptosis, flattening of the lower eyelid bags, inferior scleral show, and supplemental side effects around the eyelids; however, the rates of such occurrence might be relatively low.

Incidence of deepening of the upper eyelid sulcus in prostaglandin-associated periorbitopathy with a latanoprost ophthalmic solution.

Among some local side effects of prostaglandin-associated periorbitopathy (PAP), deepening of the upper eyelid sulcus (DUES) is the most prominent clinical feature, and is one of the most significant adverse cosmetic events. Here, we prospectively investigated the incidence of DUES in Japanese open-angle glaucoma patients initially treated with latanoprost (Xalatan 0.005%) ophthalmic solution. This was an open-label prospective study. Facial photographs and subjective reports of the recognition of DUES were obtained at the beginning of latanoprost treatment and at 2, 4, and 6 months thereafter. Intraocular pressure (IOP) was measured at three consecutive visits before and after treatment with latanoprost. The incidence of DUES was evaluated objectively by three blinded investigators who compared the series of photographs. A total of 52 eyes of 52 newly diagnosed open-angle glaucoma Japanese patients (28 males, 24 females) were evaluated. The objective rate of DUES was 1/52 (2%; 95% CI 0.05 to 10.7%) at 2 months, 2/52 (4%; 95% CI 0.5 to 13.9%) at 4 months, and 3/52 (6%; 95% CI 1.2 to 16.9%) at 6 months. During this period, no patient self-reported an occurrence of DUES. Mean IOPs before and after treatment were 16.5±2.9 and 13.8±3.0 mm Hg, respectively. Latanoprost reduced the IOP significantly (P<0.0001, paired t-test). Latanoprost caused DUES rarely and had a robust IOP-lowering effect in Japanese glaucoma patients.