The purpose of this study was to identify the structural and histological effects of a Tano diamo... more The purpose of this study was to identify the structural and histological effects of a Tano diamond-dusted membrane scraper (DDMS) on the retinal surface after internal limiting membrane (ILM) abrasion in macular hole surgery. Institutional experimental study was performed in 11 eyes. All eyes underwent ILM abrasion in the operating room with a DDMS for macular hole repair as an alternative to traditional ILM peeling. Three human donor eyes underwent an identical procedure in the laboratory. Retinal tissues were removed by ILM abrasion with a DDMS during vitrectomy for macular hole repair and retinal tissues remaining in human donor eyes. Main outcome measures were microscopic and immunohistological characteristics of instrument tip tissues and retinal structure after ILM abrasion. The tips of the Tano DDMS showed evidence of cellular membranes and ILM removal. The retinas showed distinct areas of lamellar ILM removal without penetration of the retinal nerve fiber layer (RNFL). Appl...
To report the clinical course of our first 7 consecutive patients treated with intravitreal ocrip... more To report the clinical course of our first 7 consecutive patients treated with intravitreal ocriplasmin (Jetrea(®)). Retrospective case series of the first 7 patients treated with ocriplasmin between January and December 2013 at an academic tertiary care center. The average age was 78.4 years (range: 63-92). Five patients were pseudophakic and 2 patients were phakic in the injected eye. The median baseline visual acuity (VA) was 20/60 (range: 20/25 to 20/200). The median 1-month postinjection VA was 20/70, with a mean loss of 2 lines of VA among all patients. None of the patients had complete resolution of their vitreomacular traction or macular hole at 1 month of follow-up. Three patients had subsequent pars plana vitrectomy and membrane peeling surgery. The mean follow-up period for those who did not undergo vitrectomy was 9 months (range: 1-13). One patient with known ocular hypertension had an increase in intraocular pressure requiring topical pressure-lowering eyedrops. There w...
To report the unique response of a patient with exudative age-related macular degeneration who de... more To report the unique response of a patient with exudative age-related macular degeneration who developed sequential episodes of acute noninfectious uveitis following separate intravitreal injections of bevacizumab and ranibizumab. Retrospective interventional case report. Chart review. A 73-year-old white woman, who received monthly intravitreal bevacizumab injections for exudative age-related macular degeneration in the right eye, developed decreased vision 4 days after her last injection. She had trace anterior chamber cells and 1+ vitritis, consistent with a bevacizumab-associated uveitis. The patient improved on topical steroids and cycloplegics. Subsequently, her exudative age-related macular degeneration was treated with monthly ranibizumab injections. Optical coherence tomography demonstrated persistent subretinal fluid despite treatment. Seven days after her 11th ranibizumab injection, she developed sudden decreased vision, 2+ anterior chamber cell, and 4+ vitritis. Presumptive treatment for an exogenous bacterial endophthalmitis was given after a vitreous biopsy was performed, which demonstrated severe sterile infiltrates that were culture negative. All injections were stopped. Three months later, the subretinal fluid had disappeared, the vitritis has nearly resolved, but some intraretinal fluid persisted. Acute noninfectious uveitis, a known risk following injection with either bevacizumab or ranibizumab, may develop sequentially in the same patient, suggesting the possibility of cross-sensitivity. Additionally, spontaneous anatomical improvement after uveitis from antibody-based vascular endothelial growth factor inhibition implies a suppressive immunomodulatory effect on vascular permeability or choroidal neovascularization. The availability of agents with alternative molecular structures, such as aflibercept, may permit additional insights into the complex relationship between choroidal neovascularization, vitritis, and innate and other immunologic processes.
To compare the long-term outcomes of peripheral retinal cryoablation to conventional treatment fo... more To compare the long-term outcomes of peripheral retinal cryoablation to conventional treatment for active pars planitis. Retrospective, interventional, comparative case series. Review at a single institution was conducted to compare the effect of cryotherapy to eyes with pars planitis to those receiving conventional therapy (topical, regionally injected or oral corticosteroid therapy). Best-corrected visual acuity (VA), complications, resolution of cystoid macular edema (CME), anterior chamber and vitreous inflammation were assessed. One hundred thirty-six eyes were treated conventionally, 50 eyes were treated with cryotherapy. Median follow-up was 60.8 months (range 8.1-223.1 months) in the cryotherapy group and 45.0 months (range 3.1-339.0 months) in the controls. There were no significant differences in baseline VA, anterior chamber and vitreous inflammation, presence of CME, and prior use of regional corticosteroid injections. VA improved over time in the cryotherapy group (slop...
IDIOPATHIC EPIRETINAL MEMBRANE AND VITREOMACULAR TRACTION PREFERRED PRACTICE PATTERN® New evidenc... more IDIOPATHIC EPIRETINAL MEMBRANE AND VITREOMACULAR TRACTION PREFERRED PRACTICE PATTERN® New evidence-based Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern® (PPP) guidelines, describing recommendations for the diagnosis, treatment, and management of patients.
RETINAL VEIN OCCLUSIONS PREFERRED PRACTICE PATTERN® New evidence-based Retinal Vein Occlusions Pr... more RETINAL VEIN OCCLUSIONS PREFERRED PRACTICE PATTERN® New evidence-based Retinal Vein Occlusions Preferred Practice Pattern® (PPP) guidelines, discussing the prognosis and risk factors of retinal vein occlusions and the treatment options.
To identify specific mutations causing North Carolina macular dystrophy (NCMD). Whole-genome sequ... more To identify specific mutations causing North Carolina macular dystrophy (NCMD). Whole-genome sequencing coupled with reverse transcription polymerase chain reaction (RT-PCR) analysis of gene expression in human retinal cells. A total of 141 members of 12 families with NCMD and 261 unrelated control individuals. Genome sequencing was performed on 8 affected individuals from 3 families affected with chromosome 6-linked NCMD (MCDR1) and 2 individuals affected with chromosome 5-linked NCMD (MCDR3). Variants observed in the MCDR1 locus with frequencies <1% in published databases were confirmed using Sanger sequencing. Confirmed variants absent from all published databases were sought in 8 additional MCDR1 families and 261 controls. The RT-PCR analysis of selected genes was performed in stem cell-derived human retinal cells. Co-segregation of rare genetic variants with disease phenotype. Five sequenced individuals with MCDR1-linked NCMD shared a haplotype of 14 rare variants spanning 1 Mb of the disease-causing allele. One of these variants (V1) was absent from all published databases and all 261 controls, but was found in 5 additional NCMD kindreds. This variant lies in a DNase 1 hypersensitivity site (DHS) upstream of both the PRDM13 and CCNC genes. Sanger sequencing of 1 kb centered on V1 was performed in the remaining 4 NCMD probands, and 2 additional novel single nucleotide variants (V2 in 3 families and V3 in 1 family) were identified in the DHS within 134 bp of the location of V1. A complete duplication of the PRDM13 gene was also discovered in a single family (V4). The RT-PCR analysis of PRDM13 expression in developing retinal cells revealed marked developmental regulation. Next-generation sequencing of 2 individuals with MCDR3-linked NCMD revealed a 900-kb duplication that included the entire IRX1 gene (V5). The 5 mutations V1 to V5 segregated perfectly in the 102 affected and 39 unaffected members of the 12 NCMD families. We identified 5 rare mutations, each capable of arresting human macular development. Four of these strongly implicate the involvement of PRDM13 in macular development, whereas the pathophysiologic mechanism of the fifth remains unknown but may involve the developmental dysregulation of IRX1.
... Coats Disease: 11-year-old male with poor vision in left eye Jason P. Brinton, MD, Lauren E. ... more ... Coats Disease: 11-year-old male with poor vision in left eye Jason P. Brinton, MD, Lauren E. Jensen, and James C. Folk, MD December 30, 2009 ... Coats' disease diagnosed in adulthood. Smithen LM, Brown GC, Brucker AJ, Yannuzzi LA, Klais CM, Spaide RF. Ophthalmology. ...
\s=b\Iris fluorescein angiography was used to perform the first prospective, controlled, masked e... more \s=b\Iris fluorescein angiography was used to perform the first prospective, controlled, masked evaluation of the effect of panretinal photocoagulation on diabetic rubeosis. Eyes with rubeosis had iris fluorescein angiograms five to seven weeks apart. Eyes either had laser treat- ment immediately after the first angio- gram or had no laser treatment between angiograms. The rubeosis was said to have improved if all three masked readers independently selected the angiogram performed last as having the less severe rubeosis. In eyes with severe rubeosis, only two of 11 (18%) spontaneously improved whereas 11 of 15 (73%) improved following laser therapy. In eyes with mild rubeosis, one of ten improved spontaneously and one of ten improved following laser therapy. Iris fluorescein angiography documented regression of severe but not mild rubeosis following panretinal photocoagulation.
Digital retinal imaging is an established method of screening for diabetic retinopathy (DR). It h... more Digital retinal imaging is an established method of screening for diabetic retinopathy (DR). It has been established that currently about 1% of the world's blind or visually impaired is due to DR. However, the increasing prevalence of diabetes mellitus and DR is creating an increased workload on those with expertise in grading retinal images. Safe and reliable automated analysis of retinal images may support screening services worldwide. This study aimed to compare the Iowa Detection Program (IDP) ability to detect diabetic eye diseases (DED) to human grading carried out at Moorfields Reading Centre on the population of Nakuru Study from Kenya. Retinal images were taken from participants of the Nakuru Eye Disease Study in Kenya in 2007/08 (n = 4,381 participants [NW6 Topcon Digital Retinal Camera]). First, human grading was performed for the presence or absence of DR, and for those with DR this was sub-divided in to referable or non-referable DR. The automated IDP software was deployed to identify those with DR and also to categorize the severity of DR. The primary outcomes were sensitivity, specificity, and positive and negative predictive value of IDP versus the human grader as reference standard. Altogether 3,460 participants were included. 113 had DED, giving a prevalence of 3.3% (95% CI, 2.7-3.9%). Sensitivity of the IDP to detect DED as by the human grading was 91.0% (95% CI, 88.0-93.4%). The IDP ability to detect DED gave an AUC of 0.878 (95% CI 0.850-0.905). It showed a negative predictive value of 98%. The IDP missed no vision threatening retinopathy in any patients and none of the false negative cases met criteria for treatment. In this epidemiological sample, the IDP's grading was comparable to that of human graders'. It therefore might be feasible to consider inclusion into usual epidemiological grading.
The purpose of this study was to identify the structural and histological effects of a Tano diamo... more The purpose of this study was to identify the structural and histological effects of a Tano diamond-dusted membrane scraper (DDMS) on the retinal surface after internal limiting membrane (ILM) abrasion in macular hole surgery. Institutional experimental study was performed in 11 eyes. All eyes underwent ILM abrasion in the operating room with a DDMS for macular hole repair as an alternative to traditional ILM peeling. Three human donor eyes underwent an identical procedure in the laboratory. Retinal tissues were removed by ILM abrasion with a DDMS during vitrectomy for macular hole repair and retinal tissues remaining in human donor eyes. Main outcome measures were microscopic and immunohistological characteristics of instrument tip tissues and retinal structure after ILM abrasion. The tips of the Tano DDMS showed evidence of cellular membranes and ILM removal. The retinas showed distinct areas of lamellar ILM removal without penetration of the retinal nerve fiber layer (RNFL). Appl...
To report the clinical course of our first 7 consecutive patients treated with intravitreal ocrip... more To report the clinical course of our first 7 consecutive patients treated with intravitreal ocriplasmin (Jetrea(®)). Retrospective case series of the first 7 patients treated with ocriplasmin between January and December 2013 at an academic tertiary care center. The average age was 78.4 years (range: 63-92). Five patients were pseudophakic and 2 patients were phakic in the injected eye. The median baseline visual acuity (VA) was 20/60 (range: 20/25 to 20/200). The median 1-month postinjection VA was 20/70, with a mean loss of 2 lines of VA among all patients. None of the patients had complete resolution of their vitreomacular traction or macular hole at 1 month of follow-up. Three patients had subsequent pars plana vitrectomy and membrane peeling surgery. The mean follow-up period for those who did not undergo vitrectomy was 9 months (range: 1-13). One patient with known ocular hypertension had an increase in intraocular pressure requiring topical pressure-lowering eyedrops. There w...
To report the unique response of a patient with exudative age-related macular degeneration who de... more To report the unique response of a patient with exudative age-related macular degeneration who developed sequential episodes of acute noninfectious uveitis following separate intravitreal injections of bevacizumab and ranibizumab. Retrospective interventional case report. Chart review. A 73-year-old white woman, who received monthly intravitreal bevacizumab injections for exudative age-related macular degeneration in the right eye, developed decreased vision 4 days after her last injection. She had trace anterior chamber cells and 1+ vitritis, consistent with a bevacizumab-associated uveitis. The patient improved on topical steroids and cycloplegics. Subsequently, her exudative age-related macular degeneration was treated with monthly ranibizumab injections. Optical coherence tomography demonstrated persistent subretinal fluid despite treatment. Seven days after her 11th ranibizumab injection, she developed sudden decreased vision, 2+ anterior chamber cell, and 4+ vitritis. Presumptive treatment for an exogenous bacterial endophthalmitis was given after a vitreous biopsy was performed, which demonstrated severe sterile infiltrates that were culture negative. All injections were stopped. Three months later, the subretinal fluid had disappeared, the vitritis has nearly resolved, but some intraretinal fluid persisted. Acute noninfectious uveitis, a known risk following injection with either bevacizumab or ranibizumab, may develop sequentially in the same patient, suggesting the possibility of cross-sensitivity. Additionally, spontaneous anatomical improvement after uveitis from antibody-based vascular endothelial growth factor inhibition implies a suppressive immunomodulatory effect on vascular permeability or choroidal neovascularization. The availability of agents with alternative molecular structures, such as aflibercept, may permit additional insights into the complex relationship between choroidal neovascularization, vitritis, and innate and other immunologic processes.
To compare the long-term outcomes of peripheral retinal cryoablation to conventional treatment fo... more To compare the long-term outcomes of peripheral retinal cryoablation to conventional treatment for active pars planitis. Retrospective, interventional, comparative case series. Review at a single institution was conducted to compare the effect of cryotherapy to eyes with pars planitis to those receiving conventional therapy (topical, regionally injected or oral corticosteroid therapy). Best-corrected visual acuity (VA), complications, resolution of cystoid macular edema (CME), anterior chamber and vitreous inflammation were assessed. One hundred thirty-six eyes were treated conventionally, 50 eyes were treated with cryotherapy. Median follow-up was 60.8 months (range 8.1-223.1 months) in the cryotherapy group and 45.0 months (range 3.1-339.0 months) in the controls. There were no significant differences in baseline VA, anterior chamber and vitreous inflammation, presence of CME, and prior use of regional corticosteroid injections. VA improved over time in the cryotherapy group (slop...
IDIOPATHIC EPIRETINAL MEMBRANE AND VITREOMACULAR TRACTION PREFERRED PRACTICE PATTERN® New evidenc... more IDIOPATHIC EPIRETINAL MEMBRANE AND VITREOMACULAR TRACTION PREFERRED PRACTICE PATTERN® New evidence-based Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern® (PPP) guidelines, describing recommendations for the diagnosis, treatment, and management of patients.
RETINAL VEIN OCCLUSIONS PREFERRED PRACTICE PATTERN® New evidence-based Retinal Vein Occlusions Pr... more RETINAL VEIN OCCLUSIONS PREFERRED PRACTICE PATTERN® New evidence-based Retinal Vein Occlusions Preferred Practice Pattern® (PPP) guidelines, discussing the prognosis and risk factors of retinal vein occlusions and the treatment options.
To identify specific mutations causing North Carolina macular dystrophy (NCMD). Whole-genome sequ... more To identify specific mutations causing North Carolina macular dystrophy (NCMD). Whole-genome sequencing coupled with reverse transcription polymerase chain reaction (RT-PCR) analysis of gene expression in human retinal cells. A total of 141 members of 12 families with NCMD and 261 unrelated control individuals. Genome sequencing was performed on 8 affected individuals from 3 families affected with chromosome 6-linked NCMD (MCDR1) and 2 individuals affected with chromosome 5-linked NCMD (MCDR3). Variants observed in the MCDR1 locus with frequencies <1% in published databases were confirmed using Sanger sequencing. Confirmed variants absent from all published databases were sought in 8 additional MCDR1 families and 261 controls. The RT-PCR analysis of selected genes was performed in stem cell-derived human retinal cells. Co-segregation of rare genetic variants with disease phenotype. Five sequenced individuals with MCDR1-linked NCMD shared a haplotype of 14 rare variants spanning 1 Mb of the disease-causing allele. One of these variants (V1) was absent from all published databases and all 261 controls, but was found in 5 additional NCMD kindreds. This variant lies in a DNase 1 hypersensitivity site (DHS) upstream of both the PRDM13 and CCNC genes. Sanger sequencing of 1 kb centered on V1 was performed in the remaining 4 NCMD probands, and 2 additional novel single nucleotide variants (V2 in 3 families and V3 in 1 family) were identified in the DHS within 134 bp of the location of V1. A complete duplication of the PRDM13 gene was also discovered in a single family (V4). The RT-PCR analysis of PRDM13 expression in developing retinal cells revealed marked developmental regulation. Next-generation sequencing of 2 individuals with MCDR3-linked NCMD revealed a 900-kb duplication that included the entire IRX1 gene (V5). The 5 mutations V1 to V5 segregated perfectly in the 102 affected and 39 unaffected members of the 12 NCMD families. We identified 5 rare mutations, each capable of arresting human macular development. Four of these strongly implicate the involvement of PRDM13 in macular development, whereas the pathophysiologic mechanism of the fifth remains unknown but may involve the developmental dysregulation of IRX1.
... Coats Disease: 11-year-old male with poor vision in left eye Jason P. Brinton, MD, Lauren E. ... more ... Coats Disease: 11-year-old male with poor vision in left eye Jason P. Brinton, MD, Lauren E. Jensen, and James C. Folk, MD December 30, 2009 ... Coats' disease diagnosed in adulthood. Smithen LM, Brown GC, Brucker AJ, Yannuzzi LA, Klais CM, Spaide RF. Ophthalmology. ...
\s=b\Iris fluorescein angiography was used to perform the first prospective, controlled, masked e... more \s=b\Iris fluorescein angiography was used to perform the first prospective, controlled, masked evaluation of the effect of panretinal photocoagulation on diabetic rubeosis. Eyes with rubeosis had iris fluorescein angiograms five to seven weeks apart. Eyes either had laser treat- ment immediately after the first angio- gram or had no laser treatment between angiograms. The rubeosis was said to have improved if all three masked readers independently selected the angiogram performed last as having the less severe rubeosis. In eyes with severe rubeosis, only two of 11 (18%) spontaneously improved whereas 11 of 15 (73%) improved following laser therapy. In eyes with mild rubeosis, one of ten improved spontaneously and one of ten improved following laser therapy. Iris fluorescein angiography documented regression of severe but not mild rubeosis following panretinal photocoagulation.
Digital retinal imaging is an established method of screening for diabetic retinopathy (DR). It h... more Digital retinal imaging is an established method of screening for diabetic retinopathy (DR). It has been established that currently about 1% of the world's blind or visually impaired is due to DR. However, the increasing prevalence of diabetes mellitus and DR is creating an increased workload on those with expertise in grading retinal images. Safe and reliable automated analysis of retinal images may support screening services worldwide. This study aimed to compare the Iowa Detection Program (IDP) ability to detect diabetic eye diseases (DED) to human grading carried out at Moorfields Reading Centre on the population of Nakuru Study from Kenya. Retinal images were taken from participants of the Nakuru Eye Disease Study in Kenya in 2007/08 (n = 4,381 participants [NW6 Topcon Digital Retinal Camera]). First, human grading was performed for the presence or absence of DR, and for those with DR this was sub-divided in to referable or non-referable DR. The automated IDP software was deployed to identify those with DR and also to categorize the severity of DR. The primary outcomes were sensitivity, specificity, and positive and negative predictive value of IDP versus the human grader as reference standard. Altogether 3,460 participants were included. 113 had DED, giving a prevalence of 3.3% (95% CI, 2.7-3.9%). Sensitivity of the IDP to detect DED as by the human grading was 91.0% (95% CI, 88.0-93.4%). The IDP ability to detect DED gave an AUC of 0.878 (95% CI 0.850-0.905). It showed a negative predictive value of 98%. The IDP missed no vision threatening retinopathy in any patients and none of the false negative cases met criteria for treatment. In this epidemiological sample, the IDP's grading was comparable to that of human graders'. It therefore might be feasible to consider inclusion into usual epidemiological grading.
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