Retinal nerve fibre layer thickness measurement reproducibility improved with spectral domain optical coherence tomography.

BACKGROUND/AIMS: To investigate retinal nerve fibre layer (RNFL) thickness measurement reproducibility using conventional time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT), and to evaluate two methods defining the optic nerve head (ONH) centring: Centred Each Time (CET) vs Centred Once (CO), in terms of RNFL thickness measurement variability on SD-OCT. METHODS: Twenty-seven eyes (14 healthy subjects) had three circumpapillary scans with TD-OCT and three raster scans (three-dimensional or 3D image data) around ONH with SD-OCT. SD-OCT images were analysed in two ways: (1) CET: ONH centre was defined on each image separately and (2) CO: ONH centre was defined on one image and exported to other images after scan registration. After defining the ONH centre, a 3.4 mm diameter virtual circular OCT was resampled on SD-OCT images to mimic the conventional circumpapillary RNFL thickness measurements taken with TD-OCT. RESULTS: CET and CO showed statistically significantly better reproducibility than TD-OCT except for 11:00 with CET. CET and CO methods showed similar reproducibility. CONCLUSIONS: SD-OCT 3D cube data generally showed better RNFL measurement reproducibility than TD-OCT. The choice of ONH centring methods did not affect RNFL measurement reproducibility.

In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT.

Non-invasive methods of probing retinal function are of interest for the early detection of retinal disease. While retinal function is traditionally directly measured with the electroretinogram (ERG), recently functional optical imaging of the retina has been demonstrated. In this manuscript, stimulus-induced, intrinsic optical scattering changes in the human retina are measured in vivo with high-speed, ultrahigh resolution optical coherence tomography (OCT) operating at 50,000 axial scans per second and ~3.3 micron axial resolution. A stimulus and measurement protocol that enables measurement of functional OCT retinal signals is described. OCT signal changes in the photoreceptors are demonstrated. Two distinct responses having different temporal and spatial properties are reported. These results are discussed in the context of optical intrinsic signals measured previously in the retina by fundus imaging and scanning laser ophthalmoscopy. Finally, challenges associated with in vivo functional retinal imaging in human subjects are discussed.

Projection OCT fundus imaging for visualising outer retinal pathology in non-exudative age-related macular degeneration.

AIMS: To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD). METHODS: A high-speed, 3.5 mum resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated. RESULTS: Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images. CONCLUSIONS: Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.

Oxidative stress and antioxidant status in older adults with early cataract.

PURPOSE: Oxidative stress and antioxidant status were determined in forty healthy men and postmenopausal women aged 50-70 years (F25, M15), who underwent concurrent eye examinations. METHODS: Blood samples were collected for analysing major well-known antioxidants by HPLC systems with UV and ECD detectors, total antioxidant performance using a fluorometry, lipid peroxidation determined by malondialdehyde using a HPLC system with a fluorescent detector and by total hydroxyoctadecadienoic acid (HODE) and F2-isoprotanes (8-iso-PGF(2alpha)) using GC-MS. RESULTS: Twenty-seven (F17, M10) of the 40 subjects were diagnosed to have early cataracts at the onset of the study, which were regarded as age appropriate lens opacities. There was no significant difference in plasma major antioxidants, total antioxidant performance, and lipid peroxidation determined by malondialdehyde as well as 8-iso-PGF(2alpha) between the groups with and without early cataract. However, isomers of 9- and 13-(Z,E)-HODE levels were significantly higher in subjects with early cataract as compared with those of non-cataract subjects (P<0.05). CONCLUSION: Our data suggest that subjects with early cataract are under increased systemic oxidative stress, which can be identified by a sensitive biomarker of lipid peroxidation, such as isomers of HODE.

Intravitreal bevacizumab (Avastin) treatment of choroidal neovascularisation in patients with angioid streaks.

OBJECTIVE: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin) as treatment for choroidal neovascularisation (CNV) associated with angioid streaks METHODS: A non-randomised, interventional case series conducted on eyes with subfoveal CNV associated with angioid streaks. Intravitreal bevacizumab (1.25 mg in 0.05 ml) was injected into nine eyes of six patients between August 2005 and December 2007. Treatment efficacy was assessed based on pre- and post-treatment visual acuity and optical coherence tomography (OCT). RESULTS: With a mean follow-up of 19 months (range 10 to 28 months), the best corrected visual acuity improved by three or more lines in four eyes (44.4%), remained within two lines of baseline in four eyes (44.4%) and decreased by three or more lines in one eye (11.1%). Central foveal thickness (CFT) measured by OCT decreased an average of 67.7 microm (range +11 to -175 microm) with an average improvement in standardised change in macular thickening of 46.6% (range -12% to +84.5%). No injection-related complications or drug-related side effects were observed. CONCLUSIONS: Intravitreal bevacizumab for the treatment of subfoveal CNV secondary to angioid streaks mildly reduced central foveal thickness with a trend toward stabilisation of visual acuity. Additional follow-up and a larger patient cohort are needed to evaluate the long-term effects of this treatment.

In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography.

Noninvasive in vivo functional optical imaging of the intact retina is demonstrated by using high-speed, ultrahigh-resolution optical coherence tomography (OCT). Imaging was performed with 2.8 microm resolution at a rate of 24,000 axial scans per second. A white-light stimulus was applied to the dark-adapted rat retina, and the average reflectivities from different intraretinal layers were monitored as a function of time. A 10%-15% increase in the average amplitude reflectance of the photoreceptor outer segments was observed in response to the stimulus. The spatial distribution of the change in the OCT signal is consistent with an increase in backscatter from the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of OCT functional imaging in the intact retina.

Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration.

AIM: To describe the appearance of the non-exudative forms of age related macular degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography (UHR-OCT). METHODS: A UHR-OCT ophthalmic imaging system, which utilises a femtosecond laser light source capable of approximately 3 mum axial resolution, was employed to obtain retinal cross sectional images of patients with non-exudative AMD. Observational studies of the resulting retinal images were performed. RESULTS: 52 eyes of 42 patients with the clinical diagnosis of non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes. In these patients, three patterns of drusen were apparent on UHR-OCT: (1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative AMD had evidence of fluid under the retina or RPE. Two of these three patients had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT. CONCLUSION: With the increased resolution of UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are more clearly defined. UHR-OCT may allow for the detection of early exudative changes not visible clinically or by angiography.

Transpupillary thermotherapy (TTT) of occult choroidal neovascularization: a retrospective, noncomparative case series of fifty-seven eyes.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of occult choroidal neovascularization. METHODS: A retrospective, noncomparative case series of 57 eyes of 52 patients who presented with occult subfoveal CNV and were treated with TTT. RESULTS: 83% of eyes were either stable (+/- one line) or showed improvement in visual acuity. 83% of eyes showed stabilization of their exudative process after one TTT treatment as evidenced by resorption of subretinal and/or intraretinal exudate or hemorrhage. Nine percent of eyes developed classic CNV during the mean follow-up time of ten months. CONCLUSIONS: TTT appears to stabilize the exudative process in eyes with occult CNV. A prospective, sham-controlled, randomized study (TTT4CNV Clinical Trial) is currently underway to directly compare TTT to the natural history of occult CNV.

Endophthalmitis after pediatric strabismus surgery.

OBJECTIVE: To report 6 cases of endophthalmitis after pediatric strabismus surgery. METHODS: Retrospective review of initial signs, clinical findings, treatment, culture results, and visual and anatomical outcomes in 6 eyes of 6 children treated at 2 tertiary care institutions between 1983 and 1998. RESULTS: Four boys and 2 girls aged 8 months to 6 years (median age, 2 years) developed lethargy and asymmetric eye redness, with or without eyelid swelling or fever, within 4 days of surgery. At diagnosis (median, postoperative day 6) clinical findings included periorbital swelling, redness and leukocoria due to vitritis, and, in some cases, hypopyon. Treatment included pars plana vitrectomy and intravitreal and systemic antibiotics in all cases. Vitreous cultures grew Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Within 6 months of strabismus surgery, visual acuity was no light perception in all eyes and 3 eyes had been enucleated. The 3 remaining eyes were prephthisical. CONCLUSIONS: Endophthalmitis after pediatric strabismus surgery is rare. Children may not recognize or verbalize symptoms. Causative organisms are virulent. Visual and anatomical outcomes are poor. Lethargy, asymmetric eye redness, eyelid swelling, or fever in the postoperative period, even if initial postoperative examination results are normal, should prompt urgent ocular examination. The diagnosis of endophthalmitis may be made when biomicroscopic or indirect ophthalmoscopic examination confirms the presence of vitreous opacification with or without hypopyon. Arch Ophthalmol. 2000;118:939-944

Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy for the treatment of occult subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration. DESIGN: A retrospective, noncomparative case series. PARTICIPANTS: Sixteen eyes of 15 consecutive patients who presented with occult subfoveal choroidal neovascularization secondary to age-related macular degeneration. INTERVENTION: After informed consent was obtained, 16 eyes of 15 patients were treated with transpupillary thermotherapy. All patients underwent pretreatment fluorescein angiography and were deemed untreatable by the Macular Photocoagulation Study standard. Transpupillary thermotherapy was delivered using a diode laser at 810 nm. A variable spot size of 1.2 mm, 2.0 mm, or 3.0 mm was used depending on the size of CNV. The diode laser was delivered through a contact lens, and treatment was initiated in one spot for 60 seconds' duration at a power range between 360 and 1000 mW. The end point was an area of no visible color change to a light-gray appearance. MAIN OUTCOME MEASURES: In all eyes, outcome was assessed by Snellen chart visual acuity and clinical examination. In 10 of 16 eyes, preoperative and postoperative fluorescein angiography and optical coherence tomography were available. In the remaining 6 of 16 eyes, exudation was measured by postoperative clinical examination alone. RESULTS: Three eyes (19%) showed a two-or-more-line improvement in visual acuity over a period of 6 to 25 months. Mean follow-up was 13 months. Visual acuity remained stable (no change or one-line improvement) in nine treated eyes (56%). The remaining four eyes (25%) showed a decline (equal to one-line worsening or greater) in visual acuity. Fifteen eyes (94%) demonstrated decreased exudation on fluorescein angiography, optical coherence tomography, and/or clinical examination. CONCLUSIONS: Transpupillary thermotherapy shows no deleterious side effects in treating occult subfoveal choroidal neovascularization. A randomized, prospective study is necessary to evaluate treatment efficacy.

Differentiation of degenerative retinoschisis from retinal detachment using optical coherence tomography.

OBJECTIVE: To assess the potential of optical coherence tomography (OCT) to differentiate retinoschisis from retinal detachment. Optical coherence tomography is a noninvasive, noncontact imaging method that produces high-resolution, cross-sectional images of ocular tissue. DESIGN: Retrospective case series. PARTICIPANTS: Thirteen eyes of 12 patients with the differential diagnosis of retinoschisis versus retinal detachment. METHODS: Differentiation between retinoschisis and retinal detachment was established from both ophthalmoscopic and OCT examinations. MAIN OUTCOME MEASURE: Ability of OCT to differentiate retinoschisis from retinal detachment was measured. RESULTS: Thirteen eyes of 12 patients with retinal elevation were examined with OCT. The cross-sectional view produced by OCT was effective in distinguishing retinoschisis from retinal detachment. Optical coherence tomography images of retinoschisis show a splitting of the neurosensory retina. The OCT images of retinal detachment show separation of full-thickness neurosensory retina from the retinal pigment epithelium band. The OCT images correlated with the clinical impression in all 13 cases. CONCLUSIONS: Based on this series of cases, OCT is a potentially useful new test that may be used to distinguish retinoschisis from rhegmatogenous retinal detachment.

Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: recommendations of the International AIDS Society-USA panel.

PURPOSE: To describe the risks, benefits, and recommended use of the ganciclovir implant for the treatment of human immunodeficiency virus-related cytomegalovirus (CMV) retinitis in the era of potent antiretroviral therapy. METHODS: A panel of physicians with expertise in the use of the ganciclovir implant and in the management of CMV retinitis was convened by the International AIDS Society-USA. The panel reviewed and discussed available data, and developed recommendations for the use of the ganciclovir implant, the surgical technique, and related management issues. Recommendations were rated according to the strength and quality of the supporting evidence. RESULTS: The effect of potent antiretroviral therapy on the immunologic status of patients with human immunodeficiency virus disease has changed the manifestation and course of CMV retinitis in many patients. The clinical management of CMV retinitis and the role of the ganciclovir implant are thus changing. Factors in the decision to choose the ganciclovir implant include the patient's potential for immunologic improvement, location and severity of CMV retinitis, and the risks and costs associated with implantation and concomitant oral ganciclovir therapy. CONCLUSIONS: The ganciclovir implant is safe and effective for the treatment of CMV retinitis. The indications for its use should be modified to account for increased patient survival and the potential for CMV retinitis to be controlled by effective antiretroviral therapy. Optimal use of the ganciclovir implant and discontinuation of therapy in selected patients with improvement in immunity may result in better long-term visual outcomes.

The progressive outer retinal necrosis syndrome: successful treatment with combination antiviral therapy.

BACKGROUND AND OBJECTIVE: To assess a two-drug combination of antiviral therapy for the progressive outer retinal necrosis syndrome (PORN), given the current poor outcome with acyclovir alone. PATIENTS AND METHODS: A retrospective review was performed on six consecutive patients who were diagnosed with PORN and were treated with various combinations of intravenous or oral plus intravenous antiviral therapy. The relative efficacies of these modalities were compared. RESULTS: Six eyes of six patients showed active retinitis at the time of presentation. Three patients had unilateral retinitis, and the remaining patients had necrotic, end-stage disease in their fellow eye. All the patients were treated with combination therapy, consisting of either ganciclovir and acyclovir (three patients), foscarnet and ganciclovir (two patients), or foscarnet and acyclovir (one patient). Standard induction doses were employed. During the combination therapy, all six eyes showed resolution of the retinitis, manifested by complete fading of the original retinal lesions and an absence of new lesion formation. At the final follow-up, the areas of prior active retinitis had resolved and remained quiescent. A mild recurrence developed in one eye when ganciclovir and foscarnet were both tapered to a single daily dose. This recurrence promptly resolved with reinduction (twice daily) dosing. Two patients maintained a visual acuity of 20/50 or better in their involved eye for the duration of follow-up (38 and 27 weeks, respectively). One patient maintained a visual acuity of 20/40 for 14 weeks. The remaining three patients had macula-off retinal detachments despite resolution of active retinitis. In addition, for the duration of follow-up, one of the three patients with unilateral disease had retinitis in the uninvolved eye; all three uninvolved fellow eyes maintained a visual acuity of 20/20. One patient had progressive optic atrophy. CONCLUSIONS: Prolonged combination antiviral therapy for PORN may successfully arrest the progression of retinitis, maintain remission, and prevent involvement of the fellow eye. Furthermore, if aggressive therapy is begun early, good vision may be preserved.

Treatment of relapsed cytomegalovirus retinitis with the sustained-release ganciclovir implant.

PURPOSE: Sustained-release ganciclovir implants are effective in delaying progression of newly diagnosed cytomegalovirus (CMV) retinitis. An uncontrolled case series was assembled to evaluate the efficacy of the intravitreal ganciclovir implant for patients with sight-threatening CMV retinitis who had previously failed to respond to intravenous ganciclovir and/or foscarnet. METHODS: Between August 1993 and March 1995, 72 eyes of 55 patients received intravitreal ganciclovir implants. Patients were examined monthly after implant surgery. RESULTS: A total of 56 eyes (77.8%) were available for evaluation after implant surgery. At the 1-month postoperative visit, 48 eyes (85.7%) of 38 patients had no progression. Implants failed to control progression at the 1-month visit in eight eyes (14.3%) of six patients receiving primary implants. A total of 32 eyes (57.1%) of 29 patients did not experience three-line loss of visual acuity through the follow-up period. The median time to three-line loss was 190 days from implantation. Four eyes (7.1%) developed visual acuity of 20/200 or worse by the 1-month follow up. The median time from implantation to development of visual acuity of 20/200 or less was 224 days. The median survival time was 376 days from study entry. The most common postoperative complication was retinal detachment, which was observed in 12 eyes receiving implants. Additional self-limiting complications included significant vitreous hemorrhage (three eyes) and hypotony maculopathy (two eyes). CONCLUSION: Ganciclovir implants were effective in delaying visual loss in a significant proportion of patients who failed ganciclovir or foscarnet therapy. A number of these patients, however, experienced visual loss. Although the implants can be effective as therapy for relapsed CMV retinitis, the efficacy does not appear to match that noted in initial CMV retinitis therapy.

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.