Elias Reichel

Imaging of Macular Diseases with Optical Coherence Tomography

BACKGROUND/PURPOSE To assess the potential of a new diagnostic technique called optical coherence tomography for imaging macular disease. Optical coherence tomography is a novel noninvasive, noncontact imaging modality which produces high depth resolution (10 microns) cross-sectional tomographs of ocular tissue. It is analogous to ultrasound, except that optical rather than acoustic reflectivity is measured. METHODS Optical coherence tomography images of the macula were obtained in 51 eyes of 44 patients with selected macular diseases. Imaging is performed in a manner compatible with slit-lamp indirect biomicroscopy so that high-resolution optical tomography may be accomplished simultaneously with normal ophthalmic examination. The time-of-flight delay of light backscattered from different layers in the retina is determined using low-coherence interferometry. Cross-sectional tomographs of the retina profiling optical reflectivity versus distance into the tissue are obtained in 2.5 seconds and with a longitudinal resolution of 10 microns. RESULTS Correlation of fundus examination and fluorescein angiography with optical coherence tomography tomographs was demonstrated in 12 eyes with the following pathologies: full- and partial-thickness macular hole, epiretinal membrane, macular edema, intraretinal exudate, idiopathic central serous chorioretinopathy, and detachments of the pigment epithelium and neurosensory retina. CONCLUSION Optical coherence tomography is potentially a powerful tool for detecting and monitoring a variety of macular diseases, including macular edema, macular holes, and detachments of the neurosensory retina and pigment epithelium.

Intravitreal triamcinolone for refractory diabetic macular edema

PURPOSE To determine if intravitreal injection of triamcinolone acetonide is safe and effective in treating diabetic macular edema unresponsive to prior laser photocoagulation. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Sixteen eyes with clinically significant diabetic macular edema (CSME) that failed to respond to at least two previous sessions of laser photocoagulation. METHODS Eyes were diagnosed with CSME and treated with at least two sessions of laser photocoagulation according to Early Treatment Diabetic Retinopathy Study guidelines. At least 6 months after initial laser therapy, the response was measured by clinical examination and optical coherence tomography (OCT). Eyes with a residual central macular thickness of more than 300 microm (normal, 200 microm) and visual loss from baseline were offered intravitreal injection of 4 mg triamcinolone acetonide. The visual and anatomic responses were observed as well as complications related to the injection procedure and corticosteroid medication. MAIN OUTCOME MEASURES Visual acuity and quantitative change in OCT macular thickening were assessed. Potential complications were monitored, including intraocular pressure response, cataract progression, retinal detachment, vitreous hemorrhage, and endophthalmitis. RESULTS All patients completed 3 months of follow-up, and 8 of 16 patients (50%) completed 6 or more months of follow-up. Mean improvement in visual acuity measured 2.4, 2.4, and 1.3 Snellen lines at the 1-, 3-, and 6-month follow-up intervals, respectively. The central macular thickness as measured by OCT decreased by 55%, 57.5%, and 38%, respectively, over these same intervals from an initial pretreatment mean of 540.3 microm (+/-96.3 microm). Intraocular pressure exceeded 21 mmHg in 5, 3, and 1 eye(s), respectively, during these intervals. One eye exhibited cataract progression at 6 months. No other complications were noted over a mean follow-up of 6.2 months. Reinjection was performed in 3 of 8 eyes after 6 months because of recurrence of macular edema. CONCLUSIONS Intravitreal triamcinolone is a promising therapeutic method for diabetic macular edema that fails to respond to conventional laser photocoagulation. Complications do not appear to be prohibitive. Further study is warranted to assess the long-term efficacy and safety, and the need for retreatment.

Topography of Diabetic Macular Edema with Optical Coherence Tomography

OBJECTIVE This study aimed to develop a protocol to screen and monitor patients with diabetic macular thickening using optical coherence tomography (OCT), a technique for high-resolution cross-sectional imaging of the retina. DESIGN A cross-sectional pilot study was conducted. PARTICIPANTS A total of 182 eyes of 107 patients with diabetic retinopathy, 55 eyes from 31 patients with diabetes but no ophthalmoscopic evidence of retinopathy, and 73 eyes from 41 healthy volunteers were studied. INTERVENTION Six optical coherence tomograms were obtained in a radial spoke pattern centered on the fovea. Retinal thickness was computed automatically from each tomogram at a total of 600 locations throughout the macula. Macular thickness was displayed geographically as a false-color topographic map and was reported numerically as averages in each of nine regions. MAIN OUTCOME MEASURES Correlation of OCT with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity was measured. RESULTS Optical coherence tomography was able to quantify the development and resolution of both foveal and extrafoveal macular thickening. The mean +/- standard deviation foveal thickness was 174 +/- 18 microns in normal eyes, 179 +/- 17 microns in diabetic eyes without retinopathy, and 256 +/- 114 microns in eyes with nonproliferative diabetic retinopathy. Foveal thickness was highly correlated among left and right eyes of normal eyes (mean +/- standard deviation difference of 6 +/- 9 microns). Foveal thickness measured by OCT correlated with visual acuity (r2 = 0.79). A single diabetic eye with no slit-lamp evidence of retinopathy showed abnormal foveal thickening on OCT. CONCLUSIONS Optical coherence tomography was a useful technique for quantifying macular thickness in patients with diabetic macular edema. The topographic mapping protocol provided geographic information on macular thickness that was intuitive and objective.

The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide

Aim: Off-label intravitreal injections of bevacizumab (Avastin) have been given for the treatment of neovascular and exudative ocular diseases since May 2005. Since then, the use of intravitreal bevacizumab has spread worldwide, but the drug-related adverse events associated with its use have been reported only in a few retrospective reviews. The International Intravitreal Bevacizumab Safety Survey was initiated to gather timely information regarding adverse events from doctors around the world via the internet. Methods: An internet-based survey was designed to identify adverse events associated with intravitreal bevacizumab treatment. The survey web address was disseminated to the international vitreoretinal community via email. Rates of adverse events were calculated from participant responses. Results: 70 centres from 12 countries reported on 7113 injections given to 5228 patients. Doctor-reported adverse events included corneal abrasion, lens injury, endophthalmitis, retinal detachment, inflammation or uveitis, cataract progression, acute vision loss, central retinal artery occlusion, subretinal haemorrhage, retinal pigment epithelium tears, blood pressure elevation, transient ischaemic attack, cerebrovascular accident and death. None of the adverse event rates exceeded 0.21%. Conclusion: Intravitreal bevacizumab is being used globally for ocular diseases. Self-reporting of adverse events after intravitreal bevacizumab injections did not show an increased rate of potential drug-related ocular or systemic events. These short-term results suggest that intravitreal bevacizumab seems to be safe.

Optical coherence tomography of age-related macular degeneration and choroidal neovascularization.

OBJECTIVE The authors used optical coherence tomography (OCT), a new technique for cross-sectional imaging of the retina, to morphologically study eyes with nonexudative and exudative age-related macular degeneration (AMD). In patients with untreated exudative AMD, OCT was compared with fluorescein angiography in the identification and classification of choroidal neovascularization (CNV). METHODS Optical coherence tomography imaging is analogous to ultrasound, except that the use of light rather than sound enables higher longitudinal resolution with a noncontact and noninvasive measurement. Optical coherence tomography was performed on 391 patients with the clinical diagnosis of AMD and was compared with conventional clinical examination to establish the cross-sectional morphology of different lesions and to develop a classification scheme for CNV. Optical coherence tomograms and fluorescein angiograms then were reviewed and correlated independently in 90 eyes of 86 patients who had exudative AMD without previous laser treatment. RESULTS Pigmentary changes, soft drusen, and detachments of the neurosensory retina and retinal pigment epithelium all had distinct presentations on OCT. Subretinal and intraretinal fluid caused changes in retinal thickness or elevation that could be quantified directly from the images. Choroidal neovascularization was evident in the tomograms as a thickening and fragmentation of a reflective layer, which corresponded to the retinal pigment epithelium and choriocapillaris. Changes in the reflection from this layer were observed during the progression of neovascularization, and after laser photocoagulation treatment. Classic CNV consistently presented with well-defined boundaries on OCT, whereas occult CNV had a variable cross-sectional appearance. CONCLUSIONS Optical coherence tomography was useful in quantitatively evaluating subretinal and intraretinal fluid, assessing possible subfoveal involvement of neovascularization, and in monitoring CNV before and after laser photocoagulation. Optical coherence tomography was unable to detect CNV beneath serous pigment epithelial detachments. Optical coherence tomography may have potential in accurately defining the boundaries in a subset of angiographically occult CNV.

Mutations within the Rhodopsin Gene in Patients with Autosomal Dominant Retinitis Pigmentosa

BACKGROUND Night blindness is an early symptom of retinitis pigmentosa. The rod photoreceptors are responsible for night vision and use rhodopsin as the photosensitive pigment. METHODS AND RESULTS We found three mutations in the human rhodopsin gene; each occurred exclusively in the affected members of some families with autosomal dominant retinitis pigmentosa. Two mutations were C-to-T transitions involving separate nucleotides of codon 347; the third was a C-to-G transversion in codon 58. Each mutation corresponded to a change in one amino acid residue in the rhodopsin molecule. None of these mutations were found in 106 unrelated normal subjects who served as controls. When the incidence of these three mutations was added to that of a previously reported mutation involving codon 23, 27 of 150 unrelated patients with autosomal dominant retinitis pigmentosa (18 percent) were found to carry one of these four defects in the rhodopsin gene. All 27 patients had abnormal rod function on monitoring of their electroretinograms. It appears that patients with the mutation involving codon 23 probably descend from a single ancestor. CONCLUSIONS In some patients with autosomal dominant retinitis pigmentosa, the disease is caused by one of a variety of mutations of the rhodopsin gene.

Intravitreal triamcinolone acetonide for macular oedema due to central retinal vein occlusion

No proved treatment exists for macular oedema secondary to central retinal vein occlusion (CRVO) despite the potential for significant visual loss in affected eyes. We report a patient with bilateral non-ischaemic CRVOs and macular oedema treated with intravitreal triamcinolone acetonide. An 80 year old woman presented with a 2 week history of acute visual loss in her left eye (LE). She had a 9 month history of poor vision in her right eye (RE). On examination, visual acuity was counting fingers RE and 20/400 LE. Intraocular pressures were 12 and 14 mm Hg, respectively. Anterior segment examination showed bilateral pseudophakia with no evidence of neovascularisation. Dilated fundus examination revealed bilateral CRVOs with macular oedema. Collateral disc vessels were present in the RE. Fluorescein angiography showed diffuse leakage and blockage from intraretinal haemorrhages in both eyes with no areas of non-perfusion (Fig 1). …

The International Vitreomacular Traction Study Group Classification of Vitreomacular Adhesion, Traction, and Macular Hole

OBJECTIVE The International Vitreomacular Traction Study (IVTS) Group was convened to develop an optical coherence tomography (OCT)-based anatomic classification system for diseases of the vitreomacular interface (VMI). DESIGN The IVTS applied their clinical experience, after reviewing the relevant literature, to support the development of a strictly anatomic OCT-based classification system. PARTICIPANTS A panel of vitreoretinal disease experts was the foundation of the International Classification System. METHODS Before the meeting, panel participants were asked to review 11 articles and to complete 3 questionnaires. The articles were preselected based on searches for comprehensive reviews covering diseases of the VMI. Responses to questionnaires and the groups opinions on definitions specified in the literature were used to guide the discussion. MAIN OUTCOME MEASURES Optical coherence tomography-based anatomic definitions and classification of vitreomacular adhesion, vitreomacular traction (VMT), and macular hole. RESULTS Vitreomacular adhesion is defined as perifoveal vitreous separation with remaining vitreomacular attachment and unperturbed foveal morphologic features. It is an OCT finding that is almost always the result of normal vitreous aging, which may lead to pathologic conditions. Vitreomacular traction is characterized by anomalous posterior vitreous detachment accompanied by anatomic distortion of the fovea, which may include pseudocysts, macular schisis, cystoid macular edema, and subretinal fluid. Vitreomacular traction can be subclassified by the diameter of vitreous attachment to the macular surface as measured by OCT, with attachment of 1500 μm or less defined as focal and attachment of more than 1500 μm as broad. When associated with other macular disease, VMT is classified as concurrent. Full-thickness macular hole (FTMH) is defined as a foveal lesion with interruption of all retinal layers from the internal limiting membrane to the retinal pigment epithelium. Full-thickness macular hole is primary if caused by vitreous traction or secondary if directly the result of pathologic characteristics other than VMT. Full-thickness macular hole is subclassified by size of the hole as determined by OCT and the presence or absence of VMT. CONCLUSIONS This classification system will support systematic diagnosis and management by creating a clinically applicable system that is predictive of therapeutic outcomes and is useful for the execution and analysis of clinical studies.

Characterization of Epiretinal Membranes Using Optical Coherence Tomography

OBJECTIVE To evaluate optical coherence tomography (OCT), a novel noncontact and noninvasive imaging technique, for the diagnosis and quantitative characterization of epiretinal membranes. METHODS Optical coherence tomography is similar to an ultrasound B-scan, except that light rather than sound is used, which enables higher resolution. Over a 2-year period, OCT was used to examine 186 eyes of 160 patients who had a diagnosis of an epiretinal membrane. Optical coherence tomograms were correlated with visual acuity, slit-lamp biomicroscopy, fluorescein angiography, and funds photography. RESULTS Based on OCT, the epiretinal membrane was clearly separated from the retina with focal points of attachment in 49 eyes and globally adherent (no observed separation) in 125 eyes. Globally adherent membranes were associated with the following features: macular pseudohole (32 eyes), a difference in optical reflectivity between the membrane and retina (65 eyes), and/or a visible membrane tuft or edge (92 eyes). The membrane was undetectable on OCT in 12 eyes. The membrane thickness (mean +/- standard deviation) was 61 +/- 28 microns in the 169 eyes in which the thickness could be measured with OCT. Mean central macular thickness measured with OCT correlated with visual acuity (R2 = 0.73). CONCLUSION Optical coherence tomography was able to provide a structural assessment of the macula that was useful in the preoperative and postoperative evaluation of epiretinal membrane surgery. Quantitative measurements and the assessment of membrane adherence with OCT may be useful in characterizing the surgical prognosis of eyes with an epiretinal membrane.

Sustained Delivery Fluocinolone Acetonide Vitreous Inserts Provide Benefit for at Least 3 Years in Patients with Diabetic Macular Edema

OBJECTIVE To assess long-term efficacy and safety of intravitreal inserts releasing 0.2 μg/d (low dose) or 0.5 μg/d (high dose) fluocinolone acetonide (FAc) in patients with diabetic macular edema (DME). DESIGN Two randomized, sham injection-controlled, double-masked, multicenter clinical trials. PARTICIPANTS Subjects with persistent DME despite ≥1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393). METHODS Subjects received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year. MAIN OUTCOME MEASURES Percentage of patients with improvement of ≥15 letters from baseline. Secondary outcomes included other parameters of visual function and foveal thickness. RESULTS At month 36, the percentage of patients who gained ≥15 in letter score using the last observation carried forward method was 28.7% (low dose) and 27.8% (high dose) in the FAc insert groups compared with 18.9% (P = 0.018) in the sham group, and considering only those patients still in the trial at month 36, it was 33.0% (low dose) and 31.9% (high dose) compared with 21.4% in the sham group (P = 0.030). Preplanned subgroup analysis demonstrated a doubling of benefit compared with sham injections in patients who reported duration of DME ≥3 years at baseline; the percentage who gained ≥15 in letter score at month 36 was 34.0% (low dose; P<0.001) or 28.8% (high dose; P = 0.002) compared with 13.4% (sham). An improvement ≥2 steps in the Early Treatment Diabetic Retinopathy Study retinopathy scale occurred in 13.7% (low dose) and 10.1% (high dose) compared with 8.9% in the sham group. Almost all phakic patients in the FAc insert groups developed cataract, but their visual benefit after cataract surgery was similar to that in pseudophakic patients. The incidence of incisional glaucoma surgery at month 36 was 4.8% in the low-dose group and 8.1% in the high-dose insert group. CONCLUSIONS In patients with DME FAc inserts provide substantial visual benefit for up to 3 years and would provide a valuable addition to the options available for patients with DME.