We describe a technique to facilitate visualization of the vitreous base, pars plana, and pars pl... more We describe a technique to facilitate visualization of the vitreous base, pars plana, and pars plicata during vitreous surgery. This technique takes advantage of an externally applied fiberoptic light source coupled with scleral depression to enable direct viewing of the ciliary processes and anterior vitreous base. No special instrumentation or alteration in pars plana vitrectomy techniques is required. We have used this technique to enhance anterior dissection during vitrectomy surgery in the aphakic and pseudophakic eye associated with proliferative vitreoretinopathy, diabetic retinopathy, epithelial down-growth syndromes, and postvitrectomy fibrin formation.
The Silicone Study is a multicenter randomized clinical trial that compares a long-acting gas wit... more The Silicone Study is a multicenter randomized clinical trial that compares a long-acting gas with silicone oil for the surgical treatment of proliferative vitreoretinopathy (PVR). As part of the study, a topographic classification of PVR has been developed that is based on the characteristic patterns of retinal distortion produced by the contraction of proliferative membranes on the retina or within the vitreous base. This classification is used to document the extent and anatomic distribution of PVR present preoperatively and to help standardize the surgical treatment. Experience has shown that this classification facilitates the identification of these membranes and their systematic dissection, and the authors therefore suggest that it be used to augment the Retina Society classification of PVR.
The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery ... more The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery system (DDS) using a computational model and a 3D model of the eye. Hydrogel DDSs loaded with vancomycin (VAN) were synthesized and release behavior was characterized in vitro. Four different compartmental and four COMSOL models of the eye were developed to describe transport into the vitreous originating from a DDS placed topically, in the subconjunctiva, subretinally, and intravitreally. The concentration of the simulated DDS was assumed to be the initial concentration of the hydrogel DDS. The simulation was executed over 1500 and 100 h for the compartmental and COMSOL models, respectively. Based on the MATLAB model, topical, subconjunctival, subretinal and vitreous administration took most (~500 h to least (0 h) amount of time to reach peak concentrations in the vitreous, respectively. All routes successfully achieved therapeutic levels of drug (0.007 mg/mL) in the vitreous. These mod...
The Silicone Study is a multicentered, randomized surgical trial designed to compare the tamponad... more The Silicone Study is a multicentered, randomized surgical trial designed to compare the tamponade effectiveness of silicone oil versus long-acting gas in the treatment of proliferative vitreoretinopathy (PVR) by vitrectomy and associated techniques. Fundus photographs are taken to provide documentation of the anatomic status of eyes proposed for entry and are graded at an independent Reading Center. This article describes the protocol for photographic documentation of PVR as a continuum of increasing pathology, in which the pathology may only be present in the anterior retina, and the retina is usually highly elevated. In a validity and reliability study, agreement between photographic and clinical observation within one step was obtained for 88% of the eyes; intra- and inter-observer agreement within one step was 85 and 80%, respectively. Differences between the surgeon's grade and the Reading Center's were caused about equally by disagreement regarding extent of fixed folds and width of the funnel. Rarely did peripheral folds not visible in the photographs appear to be the sole explanation of the disagreement. Differences among readers were concerned mainly with differentiation of true full-thickness fixed folds from folds due to simple redundancy of the detached retina. These results demonstrate that complicated retinal detachment (RD) can be photographically documented and independently assessed.
Purpose To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment... more Purpose To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment for tumor seeds in the vitreous of children with retinoblastoma. Patients and Methods An Institutional Biosafety Committee–, Institutional Review Board–, Recombinant DNA Advisory Committee–, and US Food and Drug Administration–approved phase I study used intrapatient dose escalation of adenoviral vector containing a herpes simplex thymidine kinase gene (AdV-TK) followed by systemic administration of ganciclovir to treat bilateral retinoblastoma with vitreous tumor seeding refractory to standard therapies. Vitreous tumor seeds were treated by intravitreous injection of AdV-TK adjacent to disease sites. Each injection was followed by ganciclovir delivered intravenously every 12 hours for 7 days. Results Eight patients with vitreous tumor seeds were enrolled. One patient who was treated with 108 viral particles (vp) had resolution of the tumor seeds around the injection site. The seven pat...
(three Caucasians, one Chinese; three women, one man), ranging in age from 37 to 60 years, with p... more (three Caucasians, one Chinese; three women, one man), ranging in age from 37 to 60 years, with progressive visual loss (preoperative visual acuities were 0.5, 0.25, LP+ and 1.2) and ⁄or extensive and progressive visual field defects (in all) underwent a lateral or anterior orbitotomy because of an apically located OCH. All tumours were partially removed after opening of the capsula in a piecemeal fashion. Three of them developed a retrobulbar bleeding during extubation, for which the orbits were reopened. The operation in the 4th patient, a 44-year-old woman, was complicated by profuse bleeding necessitating repeated bipolar coagulation. Final visual acuity was finger counting in 3 and no light perception in one. The incidence, clinical presentation and characteristics of orbital OCHs are nowadays well known (McNab & Wright 1989). Discussion remains on the origin of OCHs and how to deal with apically located representatives. Most OCHs present in the lateral part of the middle third of the orbit, which area is rich of vascular structures. In this region, OCHs can grow by easily pushing aside other structures (Harris 2010). These are easily accessible by an anterior or lateral orbitotomy and can be removed with subtle traction using, for instance, a cryocoagulation probe. It is this kind of OCH that has an apple shape on scans. In contrast, OCHs in the orbital apex, having a pear-shaped configuration, show a different growth pattern, in which the surrounding capsula fuses with adjacent vessels and nerves in an early stage of the disease. Total removal by orbitotomy is impeded by poor visualization, lack of manoeuvring space, excessive bleeding by traction and disruption of blood vessels, damaging of nerve vessels and the ciliary ganglion. Partial removal with or without bipolar cautery shrinkage has been suggested as an alternative procedure (McNab & Wright 1989; Harris 2010). Our experience does not support this option. Although histologic proof and size reduction was the goal of surgery in apical OCHs and these tumours were approached with minimal traction, significant bleeding during or shortly after the operation necessitated reopening of the wounds. Anaesthetic data showed no sudden increase in systemic blood pressure during or immediately after surgery. Unlike in more anteriorly located OCHs, in which the complete lesion can be removed within their capsula, the disruption of the lesion’s capsula in our four patients may be the explanation of the bleeding during or after surgery. Apparently, at least in our hands, a piecemeal OCH excision is not a viable option. Irradiation (Khan et al. 2009; Rootman et al. 2012) or a combined neurosurgical ⁄ endoscopic (Locatelli et al. 2011.) orbital approach (using neuronavigation) with microdissection and the use of an operation microscope may be better options to treat these lesions. Larger series, however, are needed to confirm this assumption.
Ophthalmic Surgery, Lasers and Imaging Retina, 1999
Tissue Plasminogen Activator (TPA) has been used as an adjunct in the surgical removal of submacu... more Tissue Plasminogen Activator (TPA) has been used as an adjunct in the surgical removal of submacular hemorrhage. It is usually used intraoperatively, but may not provide enough time for effective fibrinolysis, especially for a large hemorrhage. The present study was conducted to evaluate the efficiency and safety of preoperative use of TPA for large submacular hemorrhages. Five eyes with large submacular hemorrhage secondary to age-related macular degeneration underwent subretinal injection of TPA in the office 24 hours before surgery. All hemorrhages were less than seven days old and at least 3 mm thick. Preoperative visual acuity ranged from counting fingers to hand motion (HM). Patient follow-up ranged from 3 months to 24 months (mean, 11 months). Final visual acuity ranged from 20/30 to HM. Four of the five eyes (80%) showed improved visual acuity after surgery and 3/5 (60%) attained visual acuity of 20/200 or better. Preoperative use of TPA for drainage of large submacular hemorrhage appears to be safe and may result in efficient clot removal. The true efficacy of TPA in the treatment of submacular hemorrhage can only be proven by a prospective randomized trial.
We describe a technique to facilitate visualization of the vitreous base, pars plana, and pars pl... more We describe a technique to facilitate visualization of the vitreous base, pars plana, and pars plicata during vitreous surgery. This technique takes advantage of an externally applied fiberoptic light source coupled with scleral depression to enable direct viewing of the ciliary processes and anterior vitreous base. No special instrumentation or alteration in pars plana vitrectomy techniques is required. We have used this technique to enhance anterior dissection during vitrectomy surgery in the aphakic and pseudophakic eye associated with proliferative vitreoretinopathy, diabetic retinopathy, epithelial down-growth syndromes, and postvitrectomy fibrin formation.
The Silicone Study is a multicenter randomized clinical trial that compares a long-acting gas wit... more The Silicone Study is a multicenter randomized clinical trial that compares a long-acting gas with silicone oil for the surgical treatment of proliferative vitreoretinopathy (PVR). As part of the study, a topographic classification of PVR has been developed that is based on the characteristic patterns of retinal distortion produced by the contraction of proliferative membranes on the retina or within the vitreous base. This classification is used to document the extent and anatomic distribution of PVR present preoperatively and to help standardize the surgical treatment. Experience has shown that this classification facilitates the identification of these membranes and their systematic dissection, and the authors therefore suggest that it be used to augment the Retina Society classification of PVR.
The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery ... more The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery system (DDS) using a computational model and a 3D model of the eye. Hydrogel DDSs loaded with vancomycin (VAN) were synthesized and release behavior was characterized in vitro. Four different compartmental and four COMSOL models of the eye were developed to describe transport into the vitreous originating from a DDS placed topically, in the subconjunctiva, subretinally, and intravitreally. The concentration of the simulated DDS was assumed to be the initial concentration of the hydrogel DDS. The simulation was executed over 1500 and 100 h for the compartmental and COMSOL models, respectively. Based on the MATLAB model, topical, subconjunctival, subretinal and vitreous administration took most (~500 h to least (0 h) amount of time to reach peak concentrations in the vitreous, respectively. All routes successfully achieved therapeutic levels of drug (0.007 mg/mL) in the vitreous. These mod...
The Silicone Study is a multicentered, randomized surgical trial designed to compare the tamponad... more The Silicone Study is a multicentered, randomized surgical trial designed to compare the tamponade effectiveness of silicone oil versus long-acting gas in the treatment of proliferative vitreoretinopathy (PVR) by vitrectomy and associated techniques. Fundus photographs are taken to provide documentation of the anatomic status of eyes proposed for entry and are graded at an independent Reading Center. This article describes the protocol for photographic documentation of PVR as a continuum of increasing pathology, in which the pathology may only be present in the anterior retina, and the retina is usually highly elevated. In a validity and reliability study, agreement between photographic and clinical observation within one step was obtained for 88% of the eyes; intra- and inter-observer agreement within one step was 85 and 80%, respectively. Differences between the surgeon's grade and the Reading Center's were caused about equally by disagreement regarding extent of fixed folds and width of the funnel. Rarely did peripheral folds not visible in the photographs appear to be the sole explanation of the disagreement. Differences among readers were concerned mainly with differentiation of true full-thickness fixed folds from folds due to simple redundancy of the detached retina. These results demonstrate that complicated retinal detachment (RD) can be photographically documented and independently assessed.
Purpose To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment... more Purpose To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment for tumor seeds in the vitreous of children with retinoblastoma. Patients and Methods An Institutional Biosafety Committee–, Institutional Review Board–, Recombinant DNA Advisory Committee–, and US Food and Drug Administration–approved phase I study used intrapatient dose escalation of adenoviral vector containing a herpes simplex thymidine kinase gene (AdV-TK) followed by systemic administration of ganciclovir to treat bilateral retinoblastoma with vitreous tumor seeding refractory to standard therapies. Vitreous tumor seeds were treated by intravitreous injection of AdV-TK adjacent to disease sites. Each injection was followed by ganciclovir delivered intravenously every 12 hours for 7 days. Results Eight patients with vitreous tumor seeds were enrolled. One patient who was treated with 108 viral particles (vp) had resolution of the tumor seeds around the injection site. The seven pat...
(three Caucasians, one Chinese; three women, one man), ranging in age from 37 to 60 years, with p... more (three Caucasians, one Chinese; three women, one man), ranging in age from 37 to 60 years, with progressive visual loss (preoperative visual acuities were 0.5, 0.25, LP+ and 1.2) and ⁄or extensive and progressive visual field defects (in all) underwent a lateral or anterior orbitotomy because of an apically located OCH. All tumours were partially removed after opening of the capsula in a piecemeal fashion. Three of them developed a retrobulbar bleeding during extubation, for which the orbits were reopened. The operation in the 4th patient, a 44-year-old woman, was complicated by profuse bleeding necessitating repeated bipolar coagulation. Final visual acuity was finger counting in 3 and no light perception in one. The incidence, clinical presentation and characteristics of orbital OCHs are nowadays well known (McNab & Wright 1989). Discussion remains on the origin of OCHs and how to deal with apically located representatives. Most OCHs present in the lateral part of the middle third of the orbit, which area is rich of vascular structures. In this region, OCHs can grow by easily pushing aside other structures (Harris 2010). These are easily accessible by an anterior or lateral orbitotomy and can be removed with subtle traction using, for instance, a cryocoagulation probe. It is this kind of OCH that has an apple shape on scans. In contrast, OCHs in the orbital apex, having a pear-shaped configuration, show a different growth pattern, in which the surrounding capsula fuses with adjacent vessels and nerves in an early stage of the disease. Total removal by orbitotomy is impeded by poor visualization, lack of manoeuvring space, excessive bleeding by traction and disruption of blood vessels, damaging of nerve vessels and the ciliary ganglion. Partial removal with or without bipolar cautery shrinkage has been suggested as an alternative procedure (McNab & Wright 1989; Harris 2010). Our experience does not support this option. Although histologic proof and size reduction was the goal of surgery in apical OCHs and these tumours were approached with minimal traction, significant bleeding during or shortly after the operation necessitated reopening of the wounds. Anaesthetic data showed no sudden increase in systemic blood pressure during or immediately after surgery. Unlike in more anteriorly located OCHs, in which the complete lesion can be removed within their capsula, the disruption of the lesion’s capsula in our four patients may be the explanation of the bleeding during or after surgery. Apparently, at least in our hands, a piecemeal OCH excision is not a viable option. Irradiation (Khan et al. 2009; Rootman et al. 2012) or a combined neurosurgical ⁄ endoscopic (Locatelli et al. 2011.) orbital approach (using neuronavigation) with microdissection and the use of an operation microscope may be better options to treat these lesions. Larger series, however, are needed to confirm this assumption.
Ophthalmic Surgery, Lasers and Imaging Retina, 1999
Tissue Plasminogen Activator (TPA) has been used as an adjunct in the surgical removal of submacu... more Tissue Plasminogen Activator (TPA) has been used as an adjunct in the surgical removal of submacular hemorrhage. It is usually used intraoperatively, but may not provide enough time for effective fibrinolysis, especially for a large hemorrhage. The present study was conducted to evaluate the efficiency and safety of preoperative use of TPA for large submacular hemorrhages. Five eyes with large submacular hemorrhage secondary to age-related macular degeneration underwent subretinal injection of TPA in the office 24 hours before surgery. All hemorrhages were less than seven days old and at least 3 mm thick. Preoperative visual acuity ranged from counting fingers to hand motion (HM). Patient follow-up ranged from 3 months to 24 months (mean, 11 months). Final visual acuity ranged from 20/30 to HM. Four of the five eyes (80%) showed improved visual acuity after surgery and 3/5 (60%) attained visual acuity of 20/200 or better. Preoperative use of TPA for drainage of large submacular hemorrhage appears to be safe and may result in efficient clot removal. The true efficacy of TPA in the treatment of submacular hemorrhage can only be proven by a prospective randomized trial.
Uploads
Papers by William Mieler