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.

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.

Enxerto de retalho escleral de doador como tratamento definitivo de maculopatia hipotônica pós trabeculectomia / Scleral patch as a definitive treatment for hypotonic maculopathy after trabeculectomy

RESUMO Paciente do sexo feminino, portadora de glaucoma juvenil sem controle clínico adequado, foi submetida à trabeculectomia com mitomicina C, após a qual, desenvolveu hipotensão ocular refratária às medidas conservadoras, evoluindo com um quadro de maculopatia hipotônica. Foi realizado um implante de enxerto de retalho escleral de doador sobre a fístula, com resolução do quadro e ganho de acuidade visual. A enxertia de retalho escleral de doador mostrou-se uma terapia adequada para correção da hipotensão ocular por bolha hiperfiltrante pós trabeculectomia. O cirurgião deve considerar o emprego dessa técnica ao programar a revisão destes casos.

ABSTRACT A female patient with juvenile glaucoma without clinical control underwent a trabeculectomy with mitomycin C, and developed eye hypotension which did not respond to conservative treatment, with subsequent hypotonic maculopathy. The patient was treated using a scleral patch provided by a donor above the fistula, which improved intraocular pressure and visual acuity. The use of the scleral patch above the fistula seems an adequate therapy to treat ocular hypotension due to the over-filtering trabeculectomy bubble. The surgeon should consider this technique when planning surgical solutions for such cases.

Reversible Hypotony and Choroidal Effusion Following the Use of Pergolide for Parkinson's Disease.

PURPOSE: To alert clinicians of the possibility of reversible drug-induced occult hypotony and choroidal effusion following the long-term use of pergolide. METHODS: Annotations were made while the case was observed. The clinical records of the patient were reviewed retrospectively. RESULTS: A 74-year-old Caucasian male with primary open-angle glaucoma presenting with reduced vision in both eyes and an inflamed right eye. Examination revealed bilateral hypotony, right anterior chamber inflammation, and right choroidal effusion. The right intraocular inflammation resolved completely after a short course of topical and oral antibiotics in addition to topical steroids. Nevertheless, the bilateral hypotony and right choroidal effusion persisted. Only the discontinuation of pergolide allowed the complete resolution of the patient's presenting symptoms and signs. CONCLUSIONS: Pergolide is known to cause pericardial and pleural effusion, and generalized oedema. However, its association with choroidal effusion and hypotony has never been reported.

ADRB1 and ADBR2 gene polymorphisms and the ocular hypotensive response to topical betaxolol in healthy Mexican subjects.

BACKGROUND: The ß adrenergic receptors (ADRB) are expressed in the ciliary body and trabecular meshwork, structures involved in aqueous humor production and outflow, respectively. ADRB are members of the adrenergic family of G-protein-coupled receptors. Topic ß blockers have a good local and systemic tolerance; they reduce the aqueous humor production and eye strain blocking the ADRB of the ciliary body and interfering with adenylate cyclase. However, the ocular hypotensive response is not the same in all patients and could be mediated by the polymorphisms of the ADRB genes. MATERIALS AND METHODS: Seventy-two healthy subjects were studied after treatment with topical betaxolol in both eyes. We analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing. RESULTS: There was statistically significant difference between baseline intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 ± 1.2 - follow-up IOP 13.6 ± 2.0 (mean difference-2.5 ± 1.3, p < 0.001). Gly389 had a higher baseline IOP than Arg389 (17.0 ± 1.2 mmHg versus 16.0 ± 1.2 mmHg; p = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to betaxolol therapy (-2.9 ± 1.1 mmHg versus -0.7 ± 0.4 mmHg; p < 0.001). Gln27 had a higher response than Glu27 (-2.7 ± 1.3 mmHg versus -1.9 ± 1.0; p = 0.02). CONCLUSION: Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism of the ADRB2 gene were associated with the hypotensive response to topic betaxolol in healthy Mexican volunteers.

Unusual adverse choroidal reaction to intravitreal bevacizumab in aggressive posterior retinopathy of prematurity: the Indian Twin Cities ROP screening (ITCROPS) data base report number 7.

PURPOSE: To describe a case of choroidal ischemia in a neonate after single, bilateral, intravitreal bevacizumab (IVB) injection for severe zone 1 aggressive posterior retinopathy of prematurity (AP-ROP). METHODS: A six-week-old baby, born at a gestation age of 28 weeks and birth weight of 1.08 kg, presented at a postconceptional age of 34 weeks for ROP screening. On examination, both eyes revealed engorged iris new vessels with poorly dilating pupils. Retinal examination showed media haze, severe zone 1 APROP with confluent new vessels, severe plus disease, and early vitreous condensation at the edge of new vessels for 12 clock hours. The child was treated bilaterally, with single IVB injection before laser. After 16 hours, hypotony and exudative retinal detachment with patches of choroidal whitening suggestive of choroidal ischemia were seen. RESULTS: The child was treated with topical steroids and cycloplegic drops and exudative retinal detachment resolved on the tenth day. Initial resolution of new vessels showed recurrence after two weeks and was treated with laser photocoagulation. Stable retinopathy status was noted up to six months follow-up. CONCLUSION: Choroidal ischemia secondary to a single IVB injection for the treatment of AP-ROP could be an unusual complication which raises the concern of its use as a monotherapy in neonates.

Melatonin and its analog 5-methoxycarbonylamino-N-acetyltryptamine potentiate adrenergic receptor-mediated ocular hypotensive effects in rabbits: significance for combination therapy in glaucoma.

Melatonin is currently considered a promising drug for glaucoma treatment because of its ocular hypotensive and neuroprotective effects. We have investigated the effect of melatonin and its analog 5-methoxycarbonylamino-N-acetyltryptamine, 5-MCA-NAT, on ß2/α(2A)-adrenergic receptor mRNA as well as protein expression in cultured rabbit nonpigmented ciliary epithelial cells. Quantitative polymerase chain reaction and immunocytochemical assays revealed a significant ß2-adrenergic receptor downregulation as well as α(2A)-adrenergic receptor up-regulation of treated cells (P < 0.001, maximal significant effect). In addition, we have studied the effect of these drugs upon the ocular hypotensive action of a nonselective ß-adrenergic receptor (timolol) and a selective α2-adrenergic receptor agonist (brimonidine) in normotensive rabbits. Intraocular pressure (IOP) experiments showed that the administration of timolol in rabbits pretreated with melatonin or 5-MCA-NAT evoked an additional IOP reduction of 14.02% ± 5.8% or 16.75% ± 5.48% (P < 0.01) in comparison with rabbits treated with timolol alone for 24 hours. Concerning brimonidine hypotensive action, an additional IOP reduction of 29.26% ± 5.21% or 39.07% ± 5.81% (P < 0.001) was observed in rabbits pretreated with melatonin or 5-MCA-NAT when compared with animals treated with brimonidine alone for 24 hours. Additionally, a sustained potentiating effect of a single dose of 5-MCA-NAT was seen in rabbits treated with brimonidine once daily for up 4 days (extra IOP decrease of 15.57% ± 5.15%, P < 0.05, compared with brimonidine alone). These data confirm the indirect action of melatoninergic compounds on adrenergic receptors and their remarkable effect upon the ocular hypotensive action mainly of α2-adrenergic receptor agonists but also of ß-adrenergic antagonists.

Ocular ischemia with hypotony after injection of hyaluronic acid gel.

The authors experienced a case with ocular ischemia with hypotony following injection of a dermal filler for augmentation rhinoplasty. Immediately after injection, the patient demonstrated a permanent visual loss with typical fundus features of central retinal artery occlusion. Multiple crusted ulcerative patches around the nose and left periorbit developed, and the left eye became severely inflamed, ophthalmoplegic, and hypotonic. Signs of anterior and posterior segment ischemia were observed including severe cornea edema, iris atrophy, and chorioretinal swelling. The retrograde arterial embolization of hyaluronic acid gel from vascular branches of nasal tip to central retinal artery and long posterior ciliary artery was highly suspicious. After 6 months of follow up, skin lesions and eyeball movement became normalized, but progressive exudative and tractional retinal detachment was causing phthisis bulbi.

Severe intraocular pressure fluctuation after intravitreal anti-vascular endothelial growth factor injection.

A 65-year-old man with unilateral exudative age-related macular degeneration presented initially with hypotony and a shallow choroidal detachment 5 days after an intravitreal ranibizumab injection. This was followed by an acute increase in intraocular pressure (IOP) to 60 mm Hg despite open angles, no evidence of intraocular inflammation, and no corticosteroid use. Ultrasound biomicroscopy showed a focal atrophic area in the ciliary body from the 7- to 9-o'clock positions, corresponding to the site of intravitreal injection. The IOP elevation was successfully treated with aqueous suppressants and resolved spontaneously after 48 hours. This report describes a patient with a rare case of labile IOP secondary to angle changes following ranibizumab injection. Injury to angle structures following intravitreal ranibizumab injection is a rare but potentially severe complication. Ultrasound biomicroscopy may be helpful in elucidating angle changes in the setting of labile IOP following intravitreal ranibizumab injection.

Indirect sympatholytic actions at ß-adrenoceptors account for the ocular hypotensive actions of cannabinoid receptor agonists.

Intraocular pressure (IOP) is the primary risk factor for glaucoma, a blinding eye disease. Cannabinoid agonists have long been known to decrease IOP, suggesting they may be useful in glaucoma treatment. However, the specific mechanism by which cannabinoids generate this ocular hypotensive effect remains unknown. The current evidence suggests the cannabinoids reduce IOP through actions at cannabinoid 1 (CB(1)) receptors within the eye, and adrenergic receptors (ARs) may also contribute to this action of cannabinoids. Considering this, the present study aimed to elucidate the mechanism behind the ocular hypotensive properties of cannabinoids through the use of mice genetically lacking either cannabinoid receptors or ßARs. Cannabinoid agonists, ßAR antagonists, and ßAR agonists decreased IOP in wild-type mice and CB(2)(-/-) mice. In contrast, none of these compounds were found to reduce IOP in ßAR(-/-) or CB(1)(-/-) mice. Desensitization of the ßARs and depletion of catecholamines in wild-type mice also eliminated the ability of the cannabinoid agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) to reduce IOP, strongly implicating a role for both ßARs and catecholamines in the ocular hypotensive properties of cannabinoids. Finally, CB(1) receptors were shown to colocalize with tyrosine hydroxylase, a marker for adrenergic neurons. Taken together, these findings suggest that ßARs are required for the ocular hypotensive properties of cannabinoids, and cannabinoids reduce IOP by acting as indirect sympatholytics and inhibiting norepinephrine release within the eye.

Ocular hypotony after the use of indocyanine green for epiretinal membrane surgery.

PURPOSE: To report the occurrence of transient ocular hypotony after indocyanine green (ICG)-assisted macular surgery for removal of the epiretinal membrane (ERM). MATERIALS AND METHODS: This was a retrospective review of 122 eyes of 118 patients who underwent vitrectomy for idiopathic ERM. The ICG staining technique was used in 71 eyes without fluid-air exchange (FAX) and in 15 eyes with FAX. Detailed eye examinations, including intraocular pressure (IOP) measurement, were performed before and after surgery. RESULTS: We observed postoperative transient ocular hypotony with choroidal detachment in 8 of 71 eyes (11%) in the ICG (+)/FAX (-) group, and no ocular hypotony was seen in the ICG (+)/FAX (+) group (15 eyes) or in the ICG (-) group (36 eyes). The median best corrected visual acuity (BCVA) in the ICG(-)group was only significantly better than in the ICG (+)/FAX (-) with hypotony at 1 week after surgery (p = 0.046). However, there was no statistically significant difference in BCVA at 3 and 6 months after surgery among the groups (p > 0.05). CONCLUSION: ICG staining of the internal limiting membrane (ILM) supports complete ERM removal because of enhanced visualization of the border between the ILM and the ERM. However, it should be cautioned that postoperative ocular hypotony may occur in some cases of ICG-assisted macular surgery. Therefore, informed consent with careful follow-up is required when ICG-assisted surgery is performed.

Morphine-induced ocular hypotension is modulated by nitric oxide and carbon monoxide: role of mu3 receptors.

PURPOSE: Recent findings generated from our laboratory have demonstrated the involvement of nitric oxide (NO) in morphine-induced reduction of intraocular pressure (IOP). The present study was designed to investigate the possible involvement of carbon monoxide (CO) in morphine-induced reduction of IOP and the role of mu(3) opioid receptors. METHODS: New Zealand rabbits were used in this study. They were pretreated with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 1%, 30 microL), or an inhibitor of heme oxygenase (HO), zinc protoporphyrin-IX (ZnPP-IX; 0.1 mg/kg; i.v.). The same animals were then treated with morphine (100 microg/30 microL) with or without NO or CO donors administration, sodium nitroprusside (SNP) and tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), respectively. A separate set of animals were pretreated with the nonselective opioid receptor antagonist, naloxone (100 microg/30 microL), or the micro(3) opioid receptor inhibitor, L-glutathione (GSH, 1%, 30 microL), in the presence of SNP or CORM-3 followed by morphine administration. IOP measurements were taken at different times after monolateral instillation of morphine. RESULTS: Morphine induced a significant decrease in IOP and pretreatment with ZnPP-IX or L-NAME significantly prevented this effect whereas administration of NO or CO donors amplified morphine-induced decrease in IOP. This effect was partially abrogated both by pretreatment with ZnPP-IX or L-NAME, and by pretreatment with naloxone and GSH suggesting that the decrease in IOP relies on exogenous NO and CO liberated from SNP and CORM-3, respectively. CONCLUSIONS: We conclude that the endogenous NO/CO system and micro(3) receptors contribute to morphine-induced ocular hypotension and that the reduction of IOP elicited by morphine can be augmented by exogenous NO and CO.

The safety of intraocular methotrexate in silicone-filled eyes.

BACKGROUND: Intraocular methotrexate has been safely used in eyes with primary CNS lymphoma (PCNSL), and in eyes with uveitis and proliferative diabetic retinopathy. Dosing in silicone-filled eyes was reduced from a standard 400 microg intravitreal injection due to concerns of toxicity. The present study reports the visual results of non-PCNSL, silicone-filled eyes treated with intravitreal methotrexate using cumulative dosages ranging from 200 microg to 1,200 microg. METHOD: In this retrospective case series, all patients with silicone-filled eyes who received intraocular methotrexate were included. Patients were observed with serial ophthalmic examinations. Best-corrected visual acuity was measured by Snellen acuity. Pretreatment acuities were compared to those obtained at last follow-up. RESULTS: The cohort included 12 patients (13 eyes) with disease other than PCNSL. The cumulative dose of intraocular methotrexate in any one patient ranged from 200 microg to 1,200 microg. Mean follow-up was 9 months (median, 10 months; range, 2 weeks to 16 months). Best-corrected vision at last follow-up was either stable or improved from pretreatment acuity in 12 of 13 eyes. CONCLUSION: Preservation of acuity in 12 of 13 study eyes suggests that intravitreal methotrexate in a cumulative dose of up to 1,200 microg is safe in silicone-filled eyes.

[Late postoperative choroidal detachment]. / Pózne pooperacyjne odlaczenie naczyniówki.

Three eyes of three patients with advanced primary open angle glaucoma developed hypotony and choroidal detachment 2-3 months following technically uncomplicated trabeculectomy, in one patient and facoemulsification in two patients. The two latter patients had undergone trabeculectomy previously. No wound or bleb leakage were found. Patients did not receive any antiglaucoma medications before the detachment. After treatment with topical corticosteroids and cycloplegic eyedrops both patients showed marked clinical improvement within 2-6 weeks. However, one of the patients after phacoemulsification developed recurrent choroidal detachment shortly after application of timolol drops used due to IOP elevation. Detachment resolved spontaneously after discontinuation of timolol.