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William A. Banks - One of the best experts on this subject based on the ideXlab platform.
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Disruption of the hippocampal and hypothalamic blood–brain barrier in a diet-induced obese model of type II diabetes: prevention and treatment by the mitochondrial Carbonic Anhydrase Inhibitor, topiramate
Fluids and Barriers of the CNS, 2019Co-Authors: Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. BanksAbstract:Background Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial Carbonic Anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA Inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. Methods BBB and BRB permeability were assessed using ^14C-sucrose and ^99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. Results High-fat feeding caused increased entry of ^14C-sucrose and ^99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to ^14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to ^99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of ^99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for ^14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. Conclusions Blood–brain barrier and blood–retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in ^14C-sucrose and ^99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial Carbonic Anhydrase Inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model.
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disruption of the hippocampal and hypothalamic blood brain barrier in a diet induced obese model of type ii diabetes prevention and treatment by the mitochondrial Carbonic Anhydrase Inhibitor topiramate
Fluids and Barriers of the CNS, 2019Co-Authors: Therese S. Salameh, William G. Mortell, Aric F. Logsdon, William A. Banks, Allan D ButterfieldAbstract:Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial Carbonic Anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA Inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. BBB and BRB permeability were assessed using 14C-sucrose and 99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. High-fat feeding caused increased entry of 14C-sucrose and 99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to 14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to 99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of 99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for 14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. Blood–brain barrier and blood–retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in 14C-sucrose and 99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial Carbonic Anhydrase Inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model.
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blood brain barrier disruption and neurovascular unit dysfunction in diabetic mice protection with the mitochondrial Carbonic Anhydrase Inhibitor topiramate
Journal of Pharmacology and Experimental Therapeutics, 2016Co-Authors: Therese S. Salameh, Gul N Shah, Tulin O Price, Melvin R Hayden, William A. BanksAbstract:All forms of diabetes mellitus are characterized by chronic hyperglycemia, resulting in the development of a number of microvascular and macrovascular pathologies. Diabetes is also associated with changes in brain microvasculature, leading to dysfunction and ultimately disruption of the blood-brain barrier (BBB). These changes are correlated with a decline in cognitive function. In diabetes, BBB damage is associated with increased oxidative stress and reactive oxygen species. This occurs because of the increased oxidative metabolism of glucose caused by hyperglycemia. Decreasing the production of bicarbonate with the use of a mitochondrial Carbonic Anhydrase Inhibitor (mCAi) limits oxidative metabolism and the production of reactive oxygen species. In this study, we have demonstrated that 1) streptozotocin-induced diabetes resulted in BBB disruption, 2) ultrastructural studies showed a breakdown of the BBB and changes to the neurovascular unit (NVU), including a loss of brain pericytes and retraction of astrocytes, the two cell types that maintain the BBB, and 3) treatment with topiramate, a mCAi, attenuated the effects of diabetes on BBB disruption and ultrastructural changes in the neurovascular unit.
Claudiu T Supuran - One of the best experts on this subject based on the ideXlab platform.
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polypharmacology of epacadostat a potent and selective Inhibitor of the tumor associated Carbonic Anhydrases ix and xii
Chemical Communications, 2019Co-Authors: Andrea Angeli, Claudiu T Supuran, Marta Ferraroni, Alessio Nocentini, Silvia Selleri, Paola Gratteri, Fabrizio CartaAbstract:Epacadostat (EPA), a selective indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor, has been investigated in vitro as a human (h) Carbonic Anhydrase Inhibitor (CAI). The kinetic data clearly show, for the first time, EPA to be a highly effective and selective Inhibitor for the tumor-associated isoforms hCA IX/XII. We report the high resolution X-ray crystal structure of the EPA-hCA II adduct, and assessed its binding mode to CA IX/XII by means of computational techniques. EPA may exert antitumor effects also due to the potent inhibition of the tumor-associated CAs.
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famotidine an antiulcer agent strongly inhibitshelicobacter pyloriand human Carbonic Anhydrases
ACS Medicinal Chemistry Letters, 2018Co-Authors: Andrea Angeli, Marta Ferraroni, Claudiu T SupuranAbstract:Famotidine, an antiulcer drug incorporating a sulfamide motif, was investigated as Carbonic Anhydrase Inhibitor (CAI). It acts as a nanomolar Inhibitor of several human (hCA II, VI, VII and XII) and Helicobacter pylori CAs. The high resolution X-ray structures of famotidine bound to hCA I and II revealed interesting aspects related to its CA inhibition mechanism, offering the possibility to develop antibacterials with a novel mechanism of action.
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Famotidine, an Antiulcer Agent, Strongly Inhibits Helicobacter pylori and Human Carbonic Anhydrases
2018Co-Authors: Andrea Angeli, Marta Ferraroni, Claudiu T SupuranAbstract:Famotidine, an antiulcer drug incorporating a sulfamide motif, was investigated as Carbonic Anhydrase Inhibitor (CAI). It acts as a nanomolar Inhibitor of several human (hCA II, VI, VII and XII) and Helicobacter pylori CAs. The high resolution X-ray structures of famotidine bound to hCA I and II revealed interesting aspects related to its CA inhibition mechanism, offering the possibility to develop antibacterials with a novel mechanism of action
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Discovery of Novel Nonsteroidal Anti-Inflammatory Drugs and Carbonic Anhydrase Inhibitors Hybrids (NSAIDs–CAIs) for the Management of Rheumatoid Arthritis
2018Co-Authors: Ozlem Akgul, Claudiu T Supuran, Andrea Scozzafava, Andrea Angeli, Lorenzo Di Cesare Mannelli, Daniela Vullo, Carla Ghelardini, Gianluca Bartolucci, Abdulmalik Saleh Alfawaz Altamimi, Fabrizio CartaAbstract:Herein we report the design as well as the synthesis of a new series of dual hybrid compounds consisting of the therapeutically used nonsteroidal-anti-inflammatory drugs (NSAIDs; i.e., indometacin, sulindac, ketoprofen, ibuprofen, diclofenac, ketorolac, etc., cyclooxygenase Inhibitors) and the Carbonic Anhydrase Inhibitor (CAIs) fragments of the sulfonamide type. Such compounds are proposed as new tools for the management of ache symptoms associated with rheumatoid arthritis (RA) and related inflammation diseases. The majority of the hybrids reported were effective in inhibiting the ubiquitous human (h) CA I and II as well as the RA overexpressed hCAs IX and XII isoforms, with KI values comprised of the low-medium nanomolar ranges. The antihyperalgesic activity of selected compounds was assessed by means of the paw-pressure and incapacitance tests using an in vivo RA model, and among them the hybrids 6B and 8B showed potent antinociceptive effects lasting up to 60 min after administration
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x ray crystallographic and kinetic investigations of 6 sulfamoyl saccharin as a Carbonic Anhydrase Inhibitor
Organic and Biomolecular Chemistry, 2015Co-Authors: Vincenzo Alterio, Muhammet Tanc, Jekaterina Ivanova, Raivis Zalubovskis, I V Vozny, Simona Maria Monti, A Di Fiore, G De Simone, Claudiu T SupuranAbstract:6-Sulfamoyl-saccharin was investigated as an Inhibitor of 11 α-Carbonic Anhydrase (CA, EC 4.2.1.1) isoforms of human (h) origin, hCA I–XIV, and X-ray crystallographic data were obtained for its adduct with hCA II, the physiologically dominant isoform. This compound possesses two potential zinc-binding groups, the primary sulfamoyl one and the secondary, acylatedsulfonamide. Saccharin itself binds to the Zn(II) ion from the CA active site coordinating with this last group, in deprotonated (SO2N−CO) form. Here we explain why 6-sulfamoyl-saccharin, unlike saccharin, binds to the metal ion from the hCA II active site by its primary sulfonamide moiety and not the secondary one as saccharin itself. Our study is useful for shedding new light to the structure-based drug design of isoform-selective CA Inhibitors of the sulfonamide type.
Therese S. Salameh - One of the best experts on this subject based on the ideXlab platform.
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Disruption of the hippocampal and hypothalamic blood–brain barrier in a diet-induced obese model of type II diabetes: prevention and treatment by the mitochondrial Carbonic Anhydrase Inhibitor, topiramate
Fluids and Barriers of the CNS, 2019Co-Authors: Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. BanksAbstract:Background Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial Carbonic Anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA Inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. Methods BBB and BRB permeability were assessed using ^14C-sucrose and ^99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. Results High-fat feeding caused increased entry of ^14C-sucrose and ^99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to ^14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to ^99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of ^99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for ^14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. Conclusions Blood–brain barrier and blood–retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in ^14C-sucrose and ^99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial Carbonic Anhydrase Inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model.
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disruption of the hippocampal and hypothalamic blood brain barrier in a diet induced obese model of type ii diabetes prevention and treatment by the mitochondrial Carbonic Anhydrase Inhibitor topiramate
Fluids and Barriers of the CNS, 2019Co-Authors: Therese S. Salameh, William G. Mortell, Aric F. Logsdon, William A. Banks, Allan D ButterfieldAbstract:Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial Carbonic Anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA Inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. BBB and BRB permeability were assessed using 14C-sucrose and 99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. High-fat feeding caused increased entry of 14C-sucrose and 99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to 14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to 99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of 99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for 14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. Blood–brain barrier and blood–retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in 14C-sucrose and 99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial Carbonic Anhydrase Inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model.
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blood brain barrier disruption and neurovascular unit dysfunction in diabetic mice protection with the mitochondrial Carbonic Anhydrase Inhibitor topiramate
Journal of Pharmacology and Experimental Therapeutics, 2016Co-Authors: Therese S. Salameh, Gul N Shah, Tulin O Price, Melvin R Hayden, William A. BanksAbstract:All forms of diabetes mellitus are characterized by chronic hyperglycemia, resulting in the development of a number of microvascular and macrovascular pathologies. Diabetes is also associated with changes in brain microvasculature, leading to dysfunction and ultimately disruption of the blood-brain barrier (BBB). These changes are correlated with a decline in cognitive function. In diabetes, BBB damage is associated with increased oxidative stress and reactive oxygen species. This occurs because of the increased oxidative metabolism of glucose caused by hyperglycemia. Decreasing the production of bicarbonate with the use of a mitochondrial Carbonic Anhydrase Inhibitor (mCAi) limits oxidative metabolism and the production of reactive oxygen species. In this study, we have demonstrated that 1) streptozotocin-induced diabetes resulted in BBB disruption, 2) ultrastructural studies showed a breakdown of the BBB and changes to the neurovascular unit (NVU), including a loss of brain pericytes and retraction of astrocytes, the two cell types that maintain the BBB, and 3) treatment with topiramate, a mCAi, attenuated the effects of diabetes on BBB disruption and ultrastructural changes in the neurovascular unit.
Alessio Nocentini - One of the best experts on this subject based on the ideXlab platform.
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polypharmacology of epacadostat a potent and selective Inhibitor of the tumor associated Carbonic Anhydrases ix and xii
Chemical Communications, 2019Co-Authors: Andrea Angeli, Claudiu T Supuran, Marta Ferraroni, Alessio Nocentini, Silvia Selleri, Paola Gratteri, Fabrizio CartaAbstract:Epacadostat (EPA), a selective indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor, has been investigated in vitro as a human (h) Carbonic Anhydrase Inhibitor (CAI). The kinetic data clearly show, for the first time, EPA to be a highly effective and selective Inhibitor for the tumor-associated isoforms hCA IX/XII. We report the high resolution X-ray crystal structure of the EPA-hCA II adduct, and assessed its binding mode to CA IX/XII by means of computational techniques. EPA may exert antitumor effects also due to the potent inhibition of the tumor-associated CAs.
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discovery of β adrenergic receptors blocker Carbonic Anhydrase Inhibitor hybrids for multitargeted antiglaucoma therapy
Journal of Medicinal Chemistry, 2018Co-Authors: Alessio Nocentini, Mariangela Ceruso, Silvia Bua, Carrie L. Lomelino, Jacob T. Andring, Robert Mckenna, Cecilia Lanzi, Silvia Sgambellone, Riccardo Pecori, Rosanna MatucciAbstract:The combination of a β-adrenergic receptors (AR) blocker and a Carbonic Anhydrase (CA, EC 4.2.1.1) Inhibitor in eye drops formulations is one of the most clinically used treatment for glaucoma. A novel approach consisting of single-molecule, multitargeted compounds for the treatment of glaucoma is proposed here by designing compounds which concomitantly interact with the β-adrenergic and CA targets. Most derivatives of the two series of benzenesulfonamides incorporating 2-hydroxypropylamine moieties reported here exhibited striking efficacy against the target hCA II and XII, whereas a subset of compounds also showed significant modulation of β1- and β2-ARs. X-ray crystallography studies provided rationale for the observed hCA inhibition. The best dual-agents decreased IOP more effectively than clinically used dorzolamide, timolol, and the combination of them in an animal model of glaucoma. The reported evidence supports the proof-of-concept of β-ARs blocker–CAI hybrids for antiglaucoma therapy with an inn...
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Discovery of β‑Adrenergic Receptors Blocker–Carbonic Anhydrase Inhibitor Hybrids for Multitargeted Antiglaucoma Therapy
2018Co-Authors: Alessio Nocentini, Mariangela Ceruso, Silvia Bua, Carrie L. Lomelino, Jacob T. Andring, Robert Mckenna, Cecilia Lanzi, Silvia Sgambellone, Riccardo Pecori, Rosanna MatucciAbstract:The combination of a β-adrenergic receptors (AR) blocker and a Carbonic Anhydrase (CA, EC 4.2.1.1) Inhibitor in eye drops formulations is one of the most clinically used treatment for glaucoma. A novel approach consisting of single-molecule, multitargeted compounds for the treatment of glaucoma is proposed here by designing compounds which concomitantly interact with the β-adrenergic and CA targets. Most derivatives of the two series of benzenesulfonamides incorporating 2-hydroxypropylamine moieties reported here exhibited striking efficacy against the target hCA II and XII, whereas a subset of compounds also showed significant modulation of β1- and β2-ARs. X-ray crystallography studies provided rationale for the observed hCA inhibition. The best dual-agents decreased IOP more effectively than clinically used dorzolamide, timolol, and the combination of them in an animal model of glaucoma. The reported evidence supports the proof-of-concept of β-ARs blocker–CAI hybrids for antiglaucoma therapy with an innovative mechanism of action
Gerald A. Fishman - One of the best experts on this subject based on the ideXlab platform.
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the prevalence of macular cysts in patients with clinical cone rod dystrophy determined by spectral domain optical coherence tomography
Ophthalmic Genetics, 2014Co-Authors: Serena Salvatore, Mohamed A Genead, Gerald A. FishmanAbstract:ABSTRACTBackground: To determine the prevalance of macular cysts in patients with clinical cone-rod dystrophy (CORD) using spectral-domain optical coherence tomography (SD-OCT). If macular cysts could be demonstrated in such patients, they might benefit from treatment with a Carbonic Anhydrase Inhibitor that has been shown to be effective for treating macular cysts in various night-blinding disorders.Material and Methods: Thirty-six CORD patients underwent a complete ophthalmic examination and an SD-OCT examination using two different systems. The presence of hypo-reflective lacunae was used to determine the presence of macular cysts.Results: The patients’ mean age was 42.9 ± 19.5 years (range 6–71 years). Mean BCVA was 1.09 ± 0.64 logMAR (range no light perception to 20/25 + 2 in the better-seeing eye). All the 72 eyes studied showed a variable degree of retinal thinning, disruption of what has been referred to as the inner segment ellipsoid and outer nuclear layer (ONL) thinning of the macula. None show...
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topical dorzolamide for treatment of cystoid macular edema in patients with choroideremia
Retina-the Journal of Retinal and Vitreous Diseases, 2012Co-Authors: Mohamed A Genead, Jason J Mcanany, Gerald A. FishmanAbstract:Purpose To determine the value of a topical Carbonic Anhydrase Inhibitor on the macular thickness and function in choroideremia patients with cystoid macular edema (CME).
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dorzolamide use in the management of macular cysts in a patient with enhanced s cone syndrome
Retinal Cases & Brief Reports, 2009Co-Authors: Manal Hajali, Gerald A. FishmanAbstract:PURPOSE To determine the efficacy of dorzolamide ophthalmic solution, a Carbonic Anhydrase Inhibitor, for treating macular schisis in enhanced S-cone syndrome. METHODS A 12-year-old white boy was diagnosed with enhanced S-cone syndrome based on the patient's history of night blindness, fundus examination, and electroretinogram testing that showed nondetectible rod function and atypical cone function consistent with an overabundance of blue cones. Time domain optical coherence tomography (OCT) baseline scans confirmed the presence of macular cysts, and the patient was started on dorzolamide ophthalmic drops twice a day. A Fourier domain-OCT unit was used to monitor any changes in the macular cysts. RESULTS After 8 weeks of starting the eye drops, the Fourier domain OCT showed an improvement in the macular cysts of the right eye with notable but more moderate changes in the left. Visual acuity improved one line in the right eye compared with baseline. Ten weeks later, the patient showed a further improvement in macular cysts by OCT testing in both eyes, with visual acuity improvement of one line in the left eye, and sustained one line improvement in the right. CONCLUSION The treatment of macular cysts using a topical Carbonic Anhydrase Inhibitor twice a day can potentially reduce foveal cystic changes and possibly improve visual acuity in at least some patients with enhanced S-cone syndrome.
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rebound of cystoid macular edema with continued use of acetazolamide in patients with retinitis pigmentosa
Retina-the Journal of Retinal and Vitreous Diseases, 2007Co-Authors: Marsha A Apushkin, Gerald A. Fishman, Sandeep Grover, Mark JanowiczAbstract:PURPOSE To demonstrate the presence of a rebound effect with the use of acetazolamide for the treatment of cystoid macular edema (CME) in patients with retinitis pigmentosa (RP). METHODS Six patients with RP and cystic-appearing lesions in the macula demonstrated by fluorescein angiography and/or optical coherence tomography (OCT) were treated with an oral form of Carbonic Anhydrase Inhibitor (acetazolamide [500 mg]) as a single daily dose. RESULTS All patients, treated with acetazolamide for a period of 3 weeks to 5 weeks, had initial improvement of macular edema demonstrated by OCT. However, extended use of acetazolamide, for at least 8 weeks to 12 weeks, resulted in recurrence (rebound) of CME in 3 of the 6 patients. CONCLUSIONS Results from our study suggest that rebound of CME with the continued use of acetazolamide observed by OCT may occur more frequently than previously appreciated.
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continued use of dorzolamide for the treatment of cystoid macular oedema in patients with retinitis pigmentosa
British Journal of Ophthalmology, 2007Co-Authors: Gerald A. Fishman, Marsha A ApushkinAbstract:Aim: To determine the value of a topical Carbonic Anhydrase Inhibitor for extended treatment of cystoid macular oedema (CME) in patients with retinitis pigmentosa (RP). Method: Eight patients with RP and foveal cystic-appearing lesions observed on fundus examination and by optical coherence tomography (OCT) testing were treated with a topical form of Carbonic Anhydrase Inhibitor. Results: Foveal cystic-like spaces were documented by OCT testing in all eight patients before treatment. All patients had a significant reduction in their foveal thickness (FT) and foveal zone thickness (FZT) in at least one eye after using 2% dorzolamide three times a day for 1 or 2 months. Six patients had an improvement in both eyes. After an additional 6–13 months of the same treatment regimen, out of six patients who had a sustained reduction in FT and FZT in at least one eye, four had this reduction in both eyes. While they were still taking Trusopt, a recurrence (rebound) of CME in both eyes was observed in two patients, whereas one patient had a sustained improvement in one eye and rebound of CME in the other eye. Out of 8 patients, 3 showed an improvement in their visual acuity by ⩾7 letters, in at least one eye, on Snellen acuity charts, which was determined as clinically significant. Conclusion: Results from this study suggest that patients with RP could potentially sustain a beneficial effect from continued treatment with a topical form of Carbonic Anhydrase Inhibitor.