Efficacy of Selective Laser Trabeculoplasty in Patients on Systemic Immunosuppressive Therapy.

PRCIS: When comparing patients on systemic immunosuppressive therapy to those without, there was no difference in intraocular pressure (IOP) early after SLT; however, at 1 year following SLT, IOP was higher in the immunosuppression group compared with controls. PURPOSE: To determine whether patients taking systemic immunosuppressive medications have a different IOP-lowering response to selective laser trabeculoplasty (SLT) compared with a control group of patients. METHODS: All patients who underwent SLT at Mayo Clinic 2017-2021 were identified. Patients on systemic immunosuppressive medications at the time of SLT were compared with control patients not receiving systemic immunosuppressive medications. The primary endpoints of this study were the percentage IOP reduction at 1 to 2, 3 to 6, and 12 months. Additional analyses included the percentage of patients who did not require additional therapy at each time point. RESULTS: There were 108 eyes of 72 patients that underwent SLT in the immunosuppressed group and 1997 eyes of 1417 patients in the control group. There was no significant difference in age-adjusted change in IOP between groups at the first postoperative visit 1 to 2 months following SLT (-18.8±20.7% vs. -16.0±16.5%, P =0.256) or 3-6 months following SLT (-15.2±21.6% vs. -18.3±23.2%, P =0.062). However, at 12 months following SLT, the IOP reduction in the immunosuppressive therapy group was significantly less compared with the control group (-15.1±21.2% vs. -20.3±22.9%, P =0.045). There was no difference between groups in the number of additional treatments during the study intervals. CONCLUSION: Patients in the systemic immunosuppressive therapy group showed equivalent early IOP-lowering after SLT compared with a control group, but the treatment response was diminished at 1 year. Further studies investigating IOP regulation after SLT in immunosuppressed patients are needed.

BILATERAL UVEITIS AND HYPOTONY FOLLOWING TREATMENT WITH TOPICAL CIDOFOVIR.

PURPOSE: To report a case of bilateral uveitis and hypotony associated with topical cidofovir treatment. METHODS: Case report. RESULTS: A 59-year-old diabetic man with HIV/AIDS presented with photophobia, ocular pain, and decreased vision. He was found to have bilateral hypotony, anterior uveitis, and serous choroidal detachments. Infectious disease workup, patient-reported history, and review of the patient's electronic medication list did not identify the etiology. Treatment with intensive topical corticosteroids led to resolution of uveitis and choroidal effusions within 3 months and resolution of hypotony within 9 months. Two years after his initial presentation, the patient developed acute recurrence of bilateral hypotony, anterior uveitis, and serous choroidal detachments shortly after intravenous cidofovir treatment. Careful reevaluation of the patient's outside medical records revealed that he had initiated treatment for rectal herpes simplex virus with compounded topical cidofovir one month before his initial presentation. CONCLUSION: To our knowledge, this is the first reported case of topical cidofovir causing ocular toxicity. Compounded and topical medications, like cidofovir in this case, may not appear on a patient's electronic medication list, so a focused review of outside medical records may be beneficial when a particular medication toxicity is suspected.

Effectiveness and safety of tafluprost in primary open-angle glaucoma and ocular hypertension: a post-marketing phase IV study in China.

BACKGROUND: Prostaglandin analogs (PGAs) are the first-line treatment for primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study aimed to confirm the effectiveness and safety of Tapros® (0.0015% tafluprost eye drops) in Chinese patients with POAG and OH. METHODS: This phase IV, multicenter, non-comparative, prospective study enrolled patients with POAG and OH in China between 12/27/2017 and 04/15/2020. Patients who were treatment-naïve or untreated within one month (group A) or with unreached intraocular pressure (IOP) target after previous monotherapy of other PGAs (group B) or non-PGA IOP-lowering drugs (group C) were treated with 0.0015% tafluprost for three months. The IOP reduction, response rate, and safety were observed. RESULTS: There were 165, 89, and 31 patients in groups A, B, and C, with baseline IOPs of 22.4 ± 4.7, 21.0 ± 3.5, and 22.5 ± 3.2 mmHg, respectively. The least-square means and percentages of IOP reduction at 3 months for groups A, B, and C were 4.7 (19.8%), 1.6 (6.1%), and 4.6 mmHg (20.3%), respectively. A significant reduction in IOP was observed at each visit compared with baseline (all P < 0.05). At the final visit, 57.0% of the participants in group A achieved an IOP reduction of ≥ 20%, while 40.4% and 77.4% in groups B and C achieved an IOP reduction of ≥ 10%. Fifty-eight treatment-related adverse events occurred in 46 participants (15.7%), of which the most common one was conjunctival hyperemia (34/293, 11.6%). CONCLUSIONS: Tafluprost showed a sustained and significant effect with tolerable adverse events in Chinese patients with POAG and OH who were treatment-naïve or untreated within one month or received prior treatments with unsatisfying outcomes.

Recurrent macular neurosensory detachment in hypotony maculopathy managed with topical corticosteroids.

A female patient in her late 70s underwent uncomplicated non-penetrating deep sclerectomy surgery. Three years after surgery, she presented with a sudden decrease in visual acuity, intraocular pressure (IOP) of 2 mmHg, macular folding and significant macular subretinal fluid. Assuming hypotony as the cause, topical dexamethasone was started, with complete functional and imagological improvement. Two months after withdrawal, she returned with the same symptoms and imagological findings. The same topical treatment was re-established, with progressive and complete improvement. After 14 months of follow-up and a maintenance dose of topical dexamethasone (1id), the patient remained stable with an IOP of 16 mm Hg. Hypotony maculopathy can, in rare cases, lead to subretinal fluid and neurosensory detachment. Topical corticosteroids can reverse and prevent hypotony in patients who are corticosteroid responsive. In advanced glaucoma, extremely low IOP may be as dangerous as high IOP. Timely normalisation of IOP may restore normal retinal architecture with associated functional improvement.

Severe Hypotony Maculopathy in Anterior Uveitis Associated with Hodgkin Lymphoma.

Purpose: To describe the clinical course and management of anterior uveitis complicated by ocular hypotony associated with Hodgkin lymphoma.Design: Case report.Methods: Chart and multimodal imaging review, including ultrasound biomicroscopy, widefield fundus pictures, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography.Results: A 44-year-old female with progressive visual deterioration and history of low-grade fever developed bilateral granulomatous anterior uveitis complicated by severe hypotony maculopathy, not improving with systemic and topical steroids. After starting ibopamine 2% eye drops, ocular hypotony progressively resolved with visual recovery. Histologic examination of a biopsied enlarged lymph node of the neck revealed the presence of Hodgkin lymphoma, for which the patient underwent systemic chemotherapy.Conclusion: Severe hypotony maculopathy complicating anterior uveitis can be associated with Hodgkin lymphoma. Topical ipobamine 2% was safe and effective in the treatment of ocular hypotony in this case.

The role of EP2 receptors in mediating the ultra-long-lasting intraocular pressure reduction by JV-GL1.

BACKGROUND: A single application of JV-GL1 substantially lowers non-human primate intraocular pressure (IOP) for about a week, independent of dose. This highly protracted effect does not correlate with its ocular biodisposition or correlate with the once-daily dosing regimen for other prostanoid EP2 receptor agonists such as trapenepag or omidenepag. The underlying pharmacological mechanism for the multiday extended activity of JV-GL1 is highly intriguing. The present studies were intended to determine EP2 receptor involvement in mediating the long-term ocular hypotensive activity of JV-GL1 by using mice genetically deficient in EP2 receptors. METHODS: The protracted IOP reduction produced by JV-GL1 was investigated in C57BL/6J and EP2 receptor knock-out mice (B6.129-Ptger2tm1Brey /J; EP2KO). Both ocular normotensive and steroid-induced ocular hypertensive (SI-OHT) mice were studied. IOP was measured tonometrically under general anaesthesia. Aqueous humour outflow facility was measured ex vivo using iPerfusion in normotensive C57BL/6J mouse eyes perfused with 100 nM de-esterified JV-GL1 and in SI-OHT C57BL/6J mouse eyes that had received topical JV-GL1 (0.01%) 3 days prior. RESULTS: Both the initial 1-day and the protracted multiday effects of JV-GL1 in the SI-OHT model for glaucoma were abolished by deletion of the gene encoding the EP2 receptor. Thus, JV-GL1 did not lower IOP in SI-OHT EP2KO mice, but in littermate SI-OHT EP2WT control mice, JV-GL1 statistically significantly lowered IOP for 4-6 days. CONCLUSIONS: Both the 1-day and the long-term effects of JV-GL1 on IOP are entirely EP2 receptor dependent.

Intraocular endoscopy for the evaluation and treatment of hypotony due to a traumatic cyclodialysis: a case report.

BACKGROUND: A cyclodialysis cleft often leads to direct communication between the anterior chamber and the suprachoroidal space. It is a rare condition that is encountered with blunt trauma, and less commonly, after surgery. Hypotony is the major sequelae that may lead to hypotonous maculopathy, optic disc edema, corneal folds, and astigmatism. These may cumulatively lead to visual loss. We describe how endoscopy in a cyclodialysis repair allowed us to accurately locate the cleft and guided its appropriate management avoiding unnecessary cryopexy. CASE PRESENTATION: A 41-year-old male experienced a traumatic cyclodialysis cleft, which resulted in persistent hypotony. Pars plana vitrectomy was performed to treat vitreous hemorrhage. Scleral indentation was attempted to visualize the cyclodialysis cleft. However, the depression distorted the visualization. Intraocular endoscopy was therefore used to evaluate the cleft. Guided by this assessment, only intraocular gas tamponade was used to reposition the ciliary body. The patient's intraocular pressure was restored to 13 mmHg 3 days after the operation, and OCT confirmed cleft closure 1 month after the operation. CONCLUSION: Endoscopy-assisted repair of cyclodialysis is an approach that enhances visualization and can guard against common causes of persistent cleft and hypotony, as well as reveal the causes of recurrent failure. Hence, it can eliminate unnecessary cryopexy that might worsen the hypotonous state. In our case, intraocular endoscopy was effective for the evaluation of a cyclodialysis cleft and the subsequent selection of an appropriate management technique, gas tamponade, that was more conservative than other approaches initially considered.

Rate of hypotony and intraocular pressure fluctuation immediately after intravitreal dexamethasone implantation in vitrectomized eyes.

PURPOSE: To observe the rate of hypotony and intraocular pressure (IOP) fluctuations immediately following intravitreal dexamethasone implantation in vitrectomized eyes. METHODS: The study included previously vitrectomized eyes scheduled to receive intravitreal dexamethasone implants. IOP measurements were performed at minute 1, minute 10, hour 1, hour 2, hour 3 and day 1. The primary outcome measure of the study was the rate of hypotony at the various time points, while the secondary outcome measure was the IOP profile over time. RESULTS: A total of 26 eyes were enrolled in the study. Immediately following the injection, 11 (42.3%) of the eyes exhibited an IOP<6mm Hg. Hypotony was observed in one eye (3.8%) at hour 3 and day 1. After the immediate IOP reduction, IOP recovered rapidly and showed a peak at hour 1, with 5 eyes (19.2%) exhibiting IOP levels ≥25mmHg and 1 eye (3.8%) ≥30mm Hg. Aside from the eye with persistent hypotony resulting in a choroidal effusion, no other complication was observed. CONCLUSIONS: Injection of dexamethasone implants in vitrectomized eyes resulted in immediate IOP reduction. Hypotony showed a short, self-limited course in the majority of eyes. In the presence of additional risk factors for wound incompetency, regular follow-up in the early post-injection period appears to be needed.

Dexamethasone Intravitreal Implant Injection in Eyes with Comorbid Hypotony.

PURPOSE: To evaluate outcomes in patients with hypotony treated with intravitreal dexamethasone implant (Ozurdex). DESIGN: Retrospective cohort study. PARTICIPANTS: Thirteen patients (15 eyes) that received a total of 99 dexamethasone implant injections on occasions at which the intraocular pressure was low, meeting the definition of statistical hypotony. METHODS: The medical records of 13 patients (15 consecutive eyes) receiving 1 or more intravitreal dexamethasone implants between December 2014 and April 2017 were reviewed retrospectively. Hypotony was defined as intraocular pressure less than 6.5 mmHg. The indications for intravitreal dexamethasone implant injection were intermediate or posterior uveitis (86.7%), diabetic macular edema (13.3%), and/or cystoid macular edema (6.7%). MAIN OUTCOME MEASURES: The primary outcome measures were safety outcomes and best visual acuity within 6 months of the final intravitreal dexamethasone implant injection in a hypotonous eye. RESULTS: In 15 eyes (13 patients), 99 injections were administered to eyes under circumstances of hypotony. Uveitic cystoid macular edema or diabetic macular edema was reduced after treatment in all cases. No complications were noted during the injection procedure. Three complications were noted in 2 patients after injection. Pseudophakodonesis and mild vitreous hemorrhage immediately after injection were noted in 1 patient, and a case of delayed-onset vitreous hemorrhage with pigment release was noted in another. All 3 complications resolved without intervention. The primary end point of this study-mean visual acuity-was stable over the follow-up period. In patients with hypotony whose intraocular pressure normalized during the follow-up period, this was attributable to management of glaucoma surgery-related complications rather than an effect of the intravitreal dexamethasone implant. CONCLUSIONS: Intravitreal dexamethasone implant injection is a reasonable treatment option for patients with comorbid hypotony in whom clinical findings warrant treatment with a sustained-delivery intravitreal steroid implant. Further studies, including imaging of zonules before and after intravitreal dexamethasone implant injection in a hypotonous eye, could help define risks to intraocular lens stability with this procedure.

An update on the modern management of paediatric uveitis.

Uveitis in children and young people (CYP) is often painless, chronic and persistent. It is an often silent blinding condition. Uveitis can be isolated or develop as a manifestation of a systemic disease. Due to the symptomless nature, it can present late with advanced ocular comorbidities such as band keratopathy, hypotony, cataracts. Inadequate control of the eye inflammation can result in permanent and severe ocular complications, structural damage and visual loss. One of the most common systemic associations is juvenile idiopathic arthritis where uveitis has a cumulative incidence of approximately 10%-14% (though wide variation in incidence is reported) after 5 years. Appropriately targeted uveitis screening is recommended to continue for at least 7 years in some subgroups. Paediatric uveitis poses multiple diagnostic and therapeutic challenges. Clinical manifestation and disease course may differ significantly from adult-onset uveitis. However, some CYP are still managed by adult specialists alone, without the opportunity for the prompt use of National Health Service England approved therapy. Optimal management of paediatric uveitis requires a multidisciplinary approach involving coordinated working of different specialities and healthcare professionals. This article highlights the evidence-based practice for the contemporary management of paediatric uveitis to readers in different specialities who may come across this condition. It raises awareness of early systemic treatment aiming to achieve early and complete disease inactivity thereby improving the chances of a long-term positive outcome.

Prospective study on a novel treatment for leaking cystic bleb: Efficacy and safety of collagen crosslinking.

IMPORTANCE: Management of cystic bleb leak is difficult. It would be essential to look for a method to strengthen the original pathological conjunctiva and reverse bleb leak. BACKGROUND: To evaluate the long-term efficacy and safety of collagen crosslinking in patients with leaking cystic bleb. DESIGN: Prospective interventional case series at a university-based hospital. PARTICIPANTS: Twelve eyes in 12 subjects with late-onset bleb leak from cystic bleb, without indications for prompt surgical interventions were included. METHODS: The subjects underwent crosslinking with 0.1% riboflavin application to bleb surface, followed by ultraviolet irradiation for 30 minutes. The subjects were followed up at baseline and at 1 week, 1 month, 3 months, 6 months post-treatment and then every 6 months afterwards. MAIN OUTCOME MEASURES: Interval from treatment to cessation of bleb leak, recurrence rate of bleb leak and side effects of treatment. RESULTS: The mean follow-up after crosslinking was 29.33 ± 12.45 months. Bleb leak subsided in 11 (92%) of 12 patients after a single session of crosslinking, after 1 to 8 weeks (median 3 weeks). Time to leak cessation was significantly correlated with the number of prior glaucoma interventions (R = .71, P = .014). Bleb wall at 3 months was significantly thicker than at baseline (0.70 ± 0.67 vs 0.81 ± 0.62 mm, P = .008). None of the patients experienced any complications. CONCLUSIONS AND RELEVANCE: Crosslinking achieves resolution of cystic bleb leak which lasts for at least 12 months, without the need of subsequent surgical interventions. Crosslinking is a simple, non-invasive treatment for bleb leak. It aims to restore the integrity of conjunctiva.

RKI-1447, a Rho kinase inhibitor, causes ocular hypotension, actin stress fiber disruption, and increased phagocytosis.

PURPOSE: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. METHODS: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 107 pigment particles/ml for 48 h before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. RESULT: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 h. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 h (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. CONCLUSION: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.

Geographic and Provider Variations in Ocular Hypotensive Medication Claims Among Medicare Part D Enrollees.

PURPOSE: The purpose of this study was to describe the prescribing patterns of ocular hypotensive medications by ophthalmologists and optometrists in the United States for Medicare beneficiaries. MATERIALS AND METHODS: This cross-sectional observational study examined all Medicare part D claims of ocular hypotensive medications prescribed by practicing ophthalmologists and optometrists in the United States in 2014. Claims rate was calculated as a function of the total number of Medicare part D beneficiaries within a given region. Claims rates were compared between ophthalmologists and optometrists and by region (state, and county level). The coefficient of variation was used to quantify treatment variation at the state level. RESULTS: The rates of claims for prescriptions from ophthalmologists were higher nationally than from optometrists by a 6:1 ratio. Claims rates in urban, large and small rural cities were significantly greater for ophthalmologists. Claims rates associated with optometrists were greater in isolated small rural towns. The coefficient of variation at the state level was 52.0 for optometrists, 32.6 for ophthalmologists, and 25.2 for both groups combined. CONCLUSIONS: Medicare part D claims data for ocular hypotensive medications indicate ophthalmologists used a significantly wider range of medications, derived from more medication classes and treated more patients than optometrists. A larger proportion of ocular hypotensive medication claims were associated with ophthalmologists in urban and suburban regions. The opposite was observed in isolated small rural towns. At the state level, there is a large variation in medication claims rates with the highest rates in New York and Washington, DC.

Management of Chronic Hypotony Following Bilateral Uveitis in a Patient Treated with Pembrolizumab for Cutaneous Metastatic Melanoma.

Purpose: To describe the presentation and management of severe ocular adverse events following treatment with pembrolizumab for cutaneous metastatic melanoma. Methods: Interventional case report. Results: A 73-year-old Caucasian man receiving pembrolizumab treatment for metastatic melanoma presented with panuveitis and subsequent profound hypotony, choroidal effusions, and optic disk swelling bilaterally. Oral prednisolone controlled intraocular inflammation. However, bilateral hypotony persisted which was managed over a 12-month period with ocular viscoelastic device injections into the anterior chamber of both eyes. There was also phacoemulsification with pars plana vitrectomy (PPV) and silicone oil (SO) tamponade performed on the left eye only. Intraocular pressure (IOP) stabilized (>6 mmHg) with best-corrected visual acuity of 6/60. Conclusion: We report a severe adverse event from pembrolizumab therapy resulting in uveitis and persistent hypotony. Repeat injections of high viscosity OVD achieved an increase in IOP up to 12 months. This technique may be a useful adjuvant or alternative to PPV and SO.

Identification of Bivalent Ligands with Melatonin Receptor Agonist and Fatty Acid Amide Hydrolase (FAAH) Inhibitory Activity That Exhibit Ocular Hypotensive Effect in the Rabbit.

Activation of melatonin receptors and inhibition of fatty acid amide hydrolase (FAAH) have both shown potential benefits for the treatment of glaucoma. To exploit the combination of these biological activities in single therapeutic agents, we designed dual-acting compounds sharing the pharmacophore elements required for the two targets, in search for balanced potencies as MT1/MT2 agonists and FAAH inhibitors. In particular, the N-anilinoethylamide scaffold, previously developed for melatonergic ligands, was decorated at meta position with a polymethylene linker bound to an O-arylcarbamate group, substituted according to known structure-activity relationships for FAAH inhibition. For the most active series, the N-anilinoethylamide portion was also replaced with the indole scaffold of melatonin. O-Biphenyl-3-ylcarbamate derivatives were characterized by remarkable and balanced activity at both targets, in the nanomolar range for compound 29. Topical administration reduced elevated intraocular pressure in rabbits, with a longer action and improved efficacy compared to the reference compounds melatonin and URB597.

Outcome of fixed volume intracameral sodium hyaluronate 1.4% injection for early postoperative hypotony after Baerveldt glaucoma implant.

IMPORTANCE: Using an ophthalmic viscoelastic device to manage early postoperative hypotony after Baerveldt glaucoma implant (BGI). BACKGROUND: To determine the outcome of intracameral sodium hyaluronate injection for early postoperative hypotony treatment after BGI. DESIGN: A retrospective study. PARTICIPANTS: One-hundred-and-thirty-eight patients (176 eyes) had BGI from January 2012 to November 2015. Those who had hypotony within 3 months postoperatively were studied. METHODS: Hypotonous eyes were injected with 0.1 mL sodium hyaluronate 1.4% intracameral on the slit-lamp. The patients were followed up weekly and the injection repeated up to 3 times if hypotony persisted. The tube was tied surgically as a last resort. MAIN OUTCOME MEASURES: The intraocular pressure and best-corrected visual acuity at week 1, 2, 3, 4, 6 and month 4 were assessed. RESULTS: Thirty (17.0%) out of 176 eyes developed early postoperative hypotony. The median intraocular pressure and median best-corrected visual acuity when hypotony first presented were 3 mmHg and 0.8 logMAR. Two eyes were excluded as they had more than 0.1 mL injection. Eight (29%) of the 28 hypotonous eyes resolved after one injection, seven (25%) required two and 10 (36%) needed three injections. Three (11%) eyes had surgical tube tie. The median intraocular pressures were 5, 7, 8, 10, 11 and 13 mmHg at week 1, 2, 3, 4, 6 and month 4 post-injection. The median best-corrected visual acuity were 0.60, 0.50, 0.50, 0.45, 0.40 and 0.40 logMAR for the same period. CONCLUSIONS AND RELEVANCE: Standardised intracameral 0.1 mL sodium hyaluronate 1.4% is an effective and safe way to manage early postoperative hypotony after BGI.

A case of human leukocyte antigen B-27-associated ocular hypotony successfully treated with golimumab.

A 42-year-old male presented to us after an episode of acute anterior human leukocyte antigen (HLA)-B27-associated uveitis, and intraocular pressure (IOP) in the right eye was 4 mmHg. Ultrasound biomicroscopy revealed ciliary body edema with supraciliary effusion. He was on a frequent topical corticosteroid, and oral steroid in addition to receiving a periocular injection depot corticosteroid 20 days back. He was started on treatment with subcutaneous golimumab (GLM). After a month, his IOP in the right eye was 14 mm of Hg with UBM showing resolution of ciliary body edema. GLM can be useful in the management of steroid-resistant cases of HLA B-27-associated ocular hypotony.

Chitosan coated PLGA nanoparticles amplify the ocular hypotensive effect of forskolin: Statistical design, characterization and in vivo studies.

PURPOSE: Enhancing the ocular hypotensive effect of forskolin (FK) by means of biodegradable chitosan (CS) coated poly lactic-co-glycolic acid (PLGA) nanoparticles (NP's). METHODS: One step emulsion-sonication process was employed for the formulation of CS-PLGA NP's with optimization being carried out by employing a four factor four level Box Behnken Design. The physical and spectral characterization, drug release, permeation, confocal and ocular tolerance studies (ex-vivo &in vivo) were performed. The corneal retention was assessed by gamma scintigraphic analysis and dexamethasone induced glaucamotous rabbit's intraocular pressure (IOP) was measured by means of Schiotz tonometer. RESULTS AND DISCUSSION: Particle size of optimized CS-PLGA NP's was found as 201.56 ±â€¯10.92 nm with a good PDI and positive zeta potential value. Entrapment efficiency and drug loading were found to be 72.32 ±â€¯1.12% and 28.39 ±â€¯1.67% respectively. Spectral characterization confirmed the purity and encapsulation of the drug within polymeric system. Sustained drug release and enhanced permeation profile was observed with maximum depth penetration. Ocular tolerance studies explicated its safe use. Scintigraphy studies indicated longer retention of CS-PLGA NP's while increased effectiveness after single instillation in reducing the intraocular pressure was observed. CONCLUSION: CS-PLGA-NP's could be successfully formulated and are an excellent vehicle for FK in ocular delivery.

A Novel Selective Soluble Guanylate Cyclase Activator, MGV354, Lowers Intraocular Pressure in Preclinical Models, Following Topical Ocular Dosing.

Purpose: The nitric oxide/soluble guanylate cyclase/protein kinase G (NO/sGC/PKG) is known to be involved in the regulation of intraocular pressure (IOP) and may be dysregulated in glaucoma. The purpose is to demonstrate that the sGC activator MGV354 lowers IOP in a monkey model of glaucoma and could be considered as a possible new clinical drug candidate. Methods: Changes to cGMP were assessed in primary human trabecular meshwork (hNTM) cells and binding studies were conducted using human sGC full-length protein. Ocular safety tolerability, exposure, and efficacy studies were conducted in rabbit and monkey models following topical ocular dosing of MGV354. Results: sGC was highly expressed in the human and cynomolgus monkey outflow pathways. MGV354 had a 7-fold greater Bmax to oxidized sGC compared to that of reduced sGC and generated an 8- to 10-fold greater cGMP compared to that of a reduced condition in hTM cells. A single topical ocular dose with MGV354 caused a significant dose-dependent reduction of 20% to 40% (versus vehicle), lasting up to 6 hours in pigmented rabbits and 24 hours postdose in a cynomolgus monkey model of glaucoma. The MGV354-induced IOP lowering was sustained up to 7 days following once-daily dosing in a monkey model of glaucoma and was greater in magnitude compared to Travatan (travoprost)-induced IOP reduction. Mild to moderate ocular hyperemia was the main adverse effect noted. Conclusions: MGV354 represents a novel class of sGC activators that can lower IOP in preclinical models of glaucoma. The potential for sGC activators to be used as effective IOP-lowering drugs in glaucoma patients could be further determined in clinical studies.

Severe Intraocular Pressure Elevation After Intracameral Healon 5 Viscoelastic Support for Postoperative Hypotony After XEN Gel Stent Insertion.

PURPOSE: The purpose of this article was to describe (i) a novel case of severe intraocular pressure (IOP) elevation due to intracameral Healon 5 for management of early postoperative (post-op) hypotony following XEN Gel Stent insertion and (ii) the management of this complication. MATERIALS AND METHODS: A case report. RESULTS: A 52-year-old man, with primary open-angle glaucoma and suboptimal left IOP control on maximally tolerated medical therapy, was managed with XEN Gel Stent insertion at another tertiary eye unit. Post-op, the IOP was 2 mm Hg with a shallow anterior chamber (AC) and choroidal effusions. Intracameral injections of Provisc on post-op days 1 and 3 failed to reverse hypotony. At 1 week post-op, persistent clinically significant hypotony was managed with Healon 5 injection into the AC. Twelve hours later, the patient experienced significant pain and reduced vision and presented to a different tertiary eye unit, where left visual acuity was hand movements, IOP was 70 mm Hg with a deep AC (complete ophthalmic viscosurgical device fill with Healon 5) and a flat drainage bleb with no external drainage. Emergency AC washout of the Healon 5 was performed with resolution of symptoms, visual acuity, and IOP control. CONCLUSIONS: We caution against the use of intracameral Healon 5 in the management of post-op hypotony following XEN Gel Stent insertion, given the potential risk for extreme IOP elevation and sight loss.