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1.
Eye (Lond) ; 28(10): 1231-8, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25081294

ABSTRACT

PURPOSE: To evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA). METHODS: Overall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions. Vision drop across environments was calculated, and repeatability of visual scores was determined. RESULTS: BCVA significantly reduced with decreasing contrast in all eyes. M1 scores for BCVA were greater than M2 and M3 (P<0.001); G1 scores were greater than G2 and G3 (P<0.01). BCVA dropped more in AMD eyes than in normal eyes between M1 and M2 (P=0.002) and between M1 and M3 (P=0.003). In AMD eyes, BCVA was better using ETDRS charts compared to G1 (P<0.001). The drop in visual function between ETDRS and G1 was greater in AMD eyes compared to normal eyes (P=0.004). Standard deviations of test-retest ranged from 0.100 to 0.139 logMAR. CONCLUSION: The CVA allowed analysis of the visual complaints that AMD patients experience with different lighting/contrast time-dependent conditions. BCVA changed significantly under different lighting/contrast conditions in all eyes, however, AMD eyes were more affected by contrast reduction than normal eyes. In AMD eyes, timed conditions using the CVA led to worse BCVA compared to non-timed ETDRS charts.


Subject(s)
Contrast Sensitivity/physiology , Geographic Atrophy/physiopathology , Vision Disorders/physiopathology , Visual Acuity/physiology , Wet Macular Degeneration/physiopathology , Adult , Aged , Aged, 80 and over , Female , Glare , Healthy Volunteers , Humans , Light , Male , Mesopic Vision/physiology , Middle Aged , Prospective Studies , Reproducibility of Results , Vision Tests , Young Adult
2.
Eye (Lond) ; 26(8): 1106-13, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22699975

ABSTRACT

AIM: To investigate clinical presentation and genotypes in patients with simultaneous geographic atrophy (GA) and choroidal neovascularization (CNV) and to compare with patients with GA or CNV only. PATIENTS AND METHODS: Twenty patients with combined CNV-GA and 154 CNV only and 154 GA only were chosen based on clinical exam and imaging. Six single-nucleotide polymorphisms (SNPs)-rs2274700 and rs1061170 (complement factor H), rs10490924 and rs11200638 (HTRA1/LOC387715), rs2230199 (C3), rs9332739 (C2)-were genotyped using the SNaPshot method. Chi-squared tests were used for genetic analysis. RESULTS: In patients with CNV-GA, GA progressed slowly and often preceded CNV. CNV presented as subretinal haemorrhage or fluid, with a sudden drop in visual acuity (VA). Comparing combined CNV-GA to GA and CNV only, patients with both had a higher frequency of at-risk alleles at both SNPs within the HTRA1 gene-rs10490924 (52.5%), rs11200638 (52.6%). Statistical significance was not achieved. CNV-GA patients had no protective alleles at SNP rs9332739 (C2), compared with GA (27%) and CNV only (10%). CONCLUSION: There is a paucity of reports describing simultaneous CNV-GA. Clinical and genetic results may support the fact that GA and CNV fit on an age-related macular degeneration (AMD)-disease continuum and may clarify the disease processes in AMD.


Subject(s)
Choroidal Neovascularization/genetics , Complement C2/genetics , Complement C3/genetics , Geographic Atrophy/genetics , Macular Degeneration/genetics , Polymorphism, Single Nucleotide , Serine Endopeptidases/genetics , Aged , Aged, 80 and over , Choroidal Neovascularization/physiopathology , Complement Factor H/genetics , Disease Progression , Female , Fluorescein Angiography , Gene Frequency , Genotype , Geographic Atrophy/physiopathology , High-Temperature Requirement A Serine Peptidase 1 , Humans , Macular Degeneration/physiopathology , Male , Tomography, Optical Coherence , Visual Acuity/physiology
3.
Br J Ophthalmol ; 93(5): 597-602, 2009 May.
Article in English | MEDLINE | ID: mdl-19211609

ABSTRACT

AIM: To determine whether colour or grey-scale images from high-resolution spectral optical coherence tomography (OCT) are superior in visualising clinically important details of retinal structures. METHODS: Patients with macular pathologies were imaged using spectral OCT (OTI, Toronto, Canada). Two reviewers independently analysed the retinal structures and pathologies and graded them on a four-point scale on the basis of the visibility. A third reviewer masked to the results then reviewed images where there was a different score for colour versus grey scale. RESULTS: Statistical analysis showed the grey-scale image to be significantly better in visualising the details of epiretinal membrane, photoreceptor and retinal pigment epithelium layer morphology than the colour scale image (p = 0.00088-0.0006). In 16.17% of eyes, the colour image led to the false impression of photoreceptor disruption. CONCLUSION: Grey-scale images are qualitatively superior to the colour-scale images on high-resolution spectral OCT. Colour images can be misleading, as the displayed colours are false colours, and the observer may see a dramatic change in colour and interpret that as a large change in the OCT reflectivity.


Subject(s)
Retinal Diseases/diagnosis , Color , Epiretinal Membrane/diagnosis , Epiretinal Membrane/pathology , Humans , Image Interpretation, Computer-Assisted/methods , Macular Degeneration/diagnosis , Macular Degeneration/pathology , Macular Edema/diagnosis , Macular Edema/pathology , Photoreceptor Cells, Vertebrate/pathology , Retinal Diseases/pathology , Retinal Pigment Epithelium/pathology , Retrospective Studies , Tomography, Optical Coherence/instrumentation , Tomography, Optical Coherence/methods
4.
Br J Ophthalmol ; 93(3): 366-72, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19019945

ABSTRACT

AIM: To describe vitreoretinal imaging of eyes with vitreomacular abnormalities using high-resolution coronal-plane optical coherence tomography (OCT) scanning combined with simultaneous scanning laser ophthalmoscope (SLO) imaging. METHODS: A SLO-OCT (OTI, Canada) was used to scan 835 eyes in 736 patients with vitreomacular interface abnormalities including epiretinal membranes, macular hole, incomplete posterior vitreous detachment, vitreomacular traction syndromes and diabetic and cystoid macular oedema in a retrospective study. The longitudinal-B scan images and the transverse -C scan images in the coronal plane were used to describe vitreomacular interface abnormalities. The SLO-OCT simultaneously produces a confocal image of the retina. RESULTS: The longitudinal "B" scan and en-face "C" scan images allowed identification of tractive forces of epiretinal membrane, contour of the hyaloid membrane and changes in inner retinal surface. A simultaneously obtained OCT scan and SLO image of the fundus offered exact co-localisation of retinal structures and vitreomacular interface abnormalities. CONCLUSION: Scanning the vitreomacular interface by using combined OCT and SLO enables the visualisation and better understanding of various vitreomacular interface abnormalities, due to the ability to colocalise pathology on OCT with retinal vascular landmarks and the ability to visualise pathology from a new perspective, coronal plane parallel to retinal surface.


Subject(s)
Ophthalmoscopy/methods , Retina/pathology , Retinal Diseases/diagnosis , Tomography, Optical Coherence/methods , Diabetes Complications/diagnosis , Epiretinal Membrane/diagnosis , Female , Humans , Lasers , Macular Edema/diagnosis , Male , Ophthalmoscopes , Pilot Projects , Retinal Detachment/diagnosis , Retinal Perforations/diagnosis
5.
Retin Cases Brief Rep ; 3(1): 102-4, 2009.
Article in English | MEDLINE | ID: mdl-25390855

ABSTRACT

PURPOSE: To describe the ocular manifestations of interferon induced sarcoidosis. METHODS: Observational case report. RESULTS: A 42-year-old woman with hepatitis C developed papillitis and macular edema together with cutaneous lesions 3 months after starting interferon and ribavirin therapy. The therapy was stopped. After 17 months of observation, visual acuity remained stable and papillitis and macular edema persisted. The patient was finally treated with sub-tenon's repository methyl prednisolone in the left eye which significantly resolved both macular edema and papillitis and also improved vision. CONCLUSION: Interferon induced sarcoidosis is a new entity and can have ocular manifestations such as uveitis and papillitis as one of the presenting features, which is not common.

7.
Br J Ophthalmol ; 92(5): 705-11, 2008 May.
Article in English | MEDLINE | ID: mdl-18441177

ABSTRACT

AIM: To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery. METHODS: A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology. RESULTS: No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). CONCLUSION: The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases.


Subject(s)
Drug Carriers , Nanoparticles , Vitreous Body , Animals , Biocompatible Materials , Electroretinography , Fundus Oculi , Half-Life , Injections , Materials Testing , Microscopy, Electron, Scanning , Ophthalmoscopy , Oxidation-Reduction , Porosity , Rabbits , Silicon
8.
Br J Ophthalmol ; 92(6): 810-3, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18420748

ABSTRACT

AIMS: To compare the non-decanted (standard) 4 mg versus the decanted 20 mg intravitreal triamcinolone acetonide (IVTA) injections and to assess their effect on intraocular pressure (IOP). METHODS: We retrospectively reviewed the records of 92 consecutive eyes, which received an intravitreal injection of either dose of triamcinolone acetonide, at a single retina centre. The change in IOP (elevation of at least 5 mm Hg from baseline or above 21 mm Hg) was analysed with a multivariate logistic analysis. The mean follow-up period in both groups was 27 weeks. A subgroup analysis comparing vitrectomised to non-vitrectomised eyes in both groups was also performed. RESULTS: Of the 92 eyes, 46% (23 of 51) in the 4 mg group versus 30% (12 of 41) in the 20 mg group had an IOP >21 mm of Hg (p = 0.14) after a mean follow-up period of 27 weeks. The vitrectomised eyes (3 of 24) in the 20 mg group had a significantly lower rate of IVTA induced IOP elevation than the non-vitrectomised eyes (9 of 17) (p = 0.013). The IOP elevation occurred significantly earlier in the 4 mg group (vitrectomised eyes 27 (SD 43) days and non-vitrectomised eyes 61 (52) days) than in the 20 mg group (vitrectomised eyes 104 (56) days and non-vitrectomised eyes 119 (82) days), independent of the vitreous status (vitrectomised p = 0.05 and non-vitrectomised p = 0.04). The mean value of initial high IOP in the non-vitrectomised eyes was higher in the 4 mg group than in the corresponding 20 mg group (p = 0.048). CONCLUSION: Decanted 20 mg IVTA may not pose a significantly greater risk of IOP elevation than the 4 mg non-decanted IVTA.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Ocular Hypertension/drug therapy , Triamcinolone Acetonide/administration & dosage , Drug Administration Schedule , Follow-Up Studies , Humans , Injections , Intraocular Pressure/drug effects , Multivariate Analysis , Ocular Hypertension/surgery , Retrospective Studies , Vitrectomy
9.
Eye (Lond) ; 22(11): 1384-90, 2008 Nov.
Article in English | MEDLINE | ID: mdl-17571088

ABSTRACT

PURPOSE: To compare two wavefront-sensing devices based on different principles. METHODS: Thirty-eight healthy eyes of 19 patients were measured five times in the reproducibility study. Twenty eyes of 10 patients were measured in the comparison study. The Tracey Visual Function Analyzer (VFA), based on the ray-tracing principle and the Nidek optical pathway difference (OPD)-Scan, based on the dynamic skiascopy principle were compared. Standard deviation (SD) of root mean square (RMS) errors was compared to verify the reproducibility. We evaluated RMS errors, Zernike terms and conventional refractive indexes (Sph, Cyl, Ax, and spherical equivalent). RESULTS: In RMS errors reading, both devices showed similar ratios of SD to the mean measurement value (VFA: 57.5+/-11.7%, OPD-Scan: 53.9+/-10.9%). Comparison on the same eye showed that almost all terms were significantly greater using the VFA than using the OPD-Scan. However, certain high spatial frequency aberrations (tetrafoil, pentafoil, and hexafoil) were consistently measured near zero with the OPD-Scan. CONCLUSION: Both devices showed similar level of reproducibility; however, there was considerable difference in the wavefront reading between machines when measuring the same eye. Differences in the number of sample points, centration, and measurement algorithms between the two instruments may explain our results.


Subject(s)
Lasers , Refractive Errors/diagnosis , Retinoscopes , Retinoscopy/methods , Adult , Algorithms , Corneal Topography , Equipment Design , Female , Humans , Male , Refraction, Ocular/physiology , Refractive Errors/physiopathology , Reproducibility of Results , Treatment Outcome
10.
Br J Ophthalmol ; 90(9): 1152-6, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16774958

ABSTRACT

AIMS: To investigate the safety and effectiveness of extrafoveal photodynamic therapy (PDT) occlusion of feeder vessels (FVs) in patients with subfoveal choroidal neovascularisation (CNV) as a result of age related macular degeneration. METHODS: FVs were identified using dynamic fluorescein and indocyanine green angiography with scanning laser ophthalmoscope. The standard doses of verteporfin and laser wavelength were used. The light dose was escalated by increasing the duration of the light dose so the light regimen was 50 J/cm2 for patients 1 and 2; 100 J/cm2 for patients 3, 4, 5; 125 J/cm2 for patients 6 and 7; and 150 J/cm2 for patients 8 and 9. Patients were examined at weeks 1, 4, and 12. RESULTS: The mean improvement on EDTRS chart 3 months after treatment was an increase of 2.1 lines (p = 0.07). Closure of the FV was achieved angiographically in three eyes at various light doses, in three eyes the FV was hypoperfused, and in three eyes the vessels were were neither closed nor hypoperfused. At the last follow up all FVs were reperfused. There was no evidence of retinal damage. CONCLUSION: Verteporfin enhanced FV therapy does not cause subfoveal retinal damage and may have potential to improve central vision in subfoveal CNV caused by exudative macular degeneration. It is not recommended as a monotherapy for CNV.


Subject(s)
Choroidal Neovascularization/drug therapy , Macular Degeneration/complications , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Aged , Aged, 80 and over , Choroid/blood supply , Choroidal Neovascularization/etiology , Choroidal Neovascularization/physiopathology , Female , Follow-Up Studies , Humans , Macular Degeneration/physiopathology , Male , Pilot Projects , Treatment Outcome , Verteporfin , Visual Acuity
11.
Curr Eye Res ; 31(5): 435-40, 2006 May.
Article in English | MEDLINE | ID: mdl-16714235

ABSTRACT

PURPOSE: To investigate the subretinal toxicity profile of the ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU), as well as the highest nontoxic subretinal dose of the mixture of the two agents in rat eyes. METHODS: Brown-Norway rats received subretinal injections of 1 microg, 10 microg, and 100 microg/microl PCNA-Rz and 0.06 microg/microl, 0.3 microg/microl, and 1.5 microg/microl 5-FU in the right eyes, and the left eyes were injected with H-BSS as control. Each dose was tested on 5 eyes in a 5 microl volume. In a second study, a combination of 5-FU (1.5 microg/microL) with varying 10-30-50 microg/microl doses of PCNA-Rz was tested in a regimen of four sequential subretinal injections. Toxicity was monitored by biomicroscopy, indirect ophthalmoscopy, electroretinography (ERG), and histology. RESULTS: The highest nontoxic dose for subretinal PCNA-Rz was 10 microg/microl, whereas 100 microg/microl showed disturbance of pigmentation with corresponding histological changes of retinal photoreceptor loss and retinal pigment epithelium proliferation or irregularities. Subretinal injection of all three doses of 5-FU did not show any toxicity. Serial injections of a mixture of 1.5 microg/microl 5-FU with 10 microg/microl of PCNA-Rz was found to be safe in rat eyes. CONCLUSIONS: Subretinal injections of the combination of PCNA-Rz (10 microg/microl) and 5-FU (1.5 microg/microl) demonstrated to be safe in rat eyes during the course of this study, even with a multiple administration of four injections.


Subject(s)
Fluorouracil/toxicity , Proliferating Cell Nuclear Antigen/toxicity , RNA, Catalytic/toxicity , Retina/drug effects , Animals , Drug Combinations , Electroretinography/drug effects , Injections , Male , Ophthalmoscopy , Rats , Rats, Inbred BN , Retina/ultrastructure
12.
Br J Ophthalmol ; 90(6): 705-8, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16531422

ABSTRACT

AIM: To determine the duration of residence of triamcinolone in the vitrectomised eye. METHODS: 23 eyes of 23 patients underwent intravitreal injection of high dose (20 mg) decanted triamcinolone acetonide (Kenalog) at the conclusion of vitrectomy surgery or in previously vitrectomised eyes with macular oedema from diabetes, uveitis, cataract surgery, or other surgery. RESULTS: The median time to disappearance of triamcinolone in the vitrectomised eye was 113 days (95% confidence interval (CI) 85 to 191). In the phakic eyes the median time to disappearance was 191 days (95% CI 148 to 191). In the pseudophakic eyes the median time to disappearance was 102 days (95% CI 85 to 113). This difference was not significant (p = 0.12). There were no cases of endophthalmitis or severe inflammatory reaction. Five eyes (22%) experienced intraocular pressure rise >/=10 mm Hg. CONCLUSIONS: High dose decanted intravitreal triamcinolone has a median residence time of 113 days in the vitrectomised eye. Although this appears to be shorter than in the non-vitrectomised eye, this study suggests that a sufficient duration of action will be present to be clinically useful.


Subject(s)
Anti-Inflammatory Agents/pharmacokinetics , Eye/metabolism , Glucocorticoids/pharmacokinetics , Triamcinolone Acetonide/pharmacokinetics , Vitrectomy , Aged , Female , Humans , Injections , Macular Edema/metabolism , Male , Middle Aged , Photography , Prospective Studies , Pseudophakia/metabolism , Survival Analysis , Vitreous Body
13.
Br J Ophthalmol ; 90(1): 17-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16361659

ABSTRACT

AIM: To determine the sensitivity and specificity of entoptic perimetry for diagnosing diabetic retinopathy at all levels of severity. METHODS: A prospective clinical study at the Shiley Eye Center, University of California, and San Diego. 30 patients with photographically documented diabetic retinopathy and 24 controls with a similar age distribution. Sensitivity and specificity of entoptic perimetry were computed for detecting clinically significant macular oedema within the central 120 degree radius of the fovea compared to fundus photographs. RESULTS: Entoptic perimetry can detect clinically significant diabetic retinopathy with a sensitivity of 0.88 and specificity of 1.00. Entoptic perimetry can detect the earliest stages of diabetic retinopathy with a sensitivity of 0.86. CONCLUSION: Scanning laser entoptic perimetry is an effective tool for detecting visual function loss caused by diabetic retinopathy.


Subject(s)
Diabetic Retinopathy/complications , Vision Disorders/diagnosis , Aged , Diabetic Retinopathy/physiopathology , Female , Humans , Lasers , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Vision Disorders/etiology , Vision Disorders/physiopathology , Visual Field Tests/methods , Visual Fields
14.
HIV Clin Trials ; 6(3): 136-46, 2005.
Article in English | MEDLINE | ID: mdl-16192248

ABSTRACT

BACKGROUND: Reconstitution of immune function during potent antiretroviral therapy can prompt discontinuation of maintenance cytomegalovirus (CMV) therapy but has also been associated with sight-threatening inflammatory conditions including immune recovery uveitis (IRU). METHOD: Patients with inactive CMV retinitis and a CD4+ cell count above 100/mm3, receiving CMV therapy and stable combination antiretroviral therapy, were assigned to one of two groups based on willingness to discontinue CMV therapy. RESULTS: Thirty-eight participants were enrolled: 28 discontinued anti-CMV therapy (Group 1) and 10 continued CMV treatment (Group 2). Median on-study follow-up was 16 months. One Group 1 participant who experienced an increase in plasma HIV viral load and a decline in CD4+ cell count developed confirmed progression of CMV retinitis. Progression or reactivation CMV retinitis was not observed among Group 2. IRU was present at study entry in 3 participants. Six participants in Group 1 and 3 participants in Group 2 developed IRU on-study. CMV viremia was not detected in any participants, and urinary shedding of CMV was intermittent. CONCLUSION: Recurrence of CMV retinitis following discontinuation of anti-CMV therapy among patients with antiretroviral-induced increases in CD4+ cell count was rare. However, IRU was common in both those who maintained and discontinued anti-CMV therapy.


Subject(s)
Antiviral Agents/therapeutic use , Cytomegalovirus Retinitis/drug therapy , Cytomegalovirus Retinitis/immunology , Cytomegalovirus/immunology , HIV Infections/complications , HIV-1/immunology , Uveitis/immunology , Adult , CD4 Lymphocyte Count , Cytomegalovirus Retinitis/complications , Cytomegalovirus Retinitis/virology , Female , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Humans , Male , Middle Aged , Prospective Studies , RNA, Viral/blood , Recurrence , Substance Withdrawal Syndrome/immunology , Uveitis/complications , Uveitis/virology
15.
Br J Ophthalmol ; 89(8): 1026-30, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16024859

ABSTRACT

AIMS: To improve visualisation of angiographic features in patients with age related macular degeneration associated with choroidal neovascularisation (CNV) and related complications. To evaluate if image averaging can achieve this goal. METHODS: 27 eyes of 20 sequential patients with age related macular degeneration over a 3 month period were studied. Indocyanine green angiograms (ICGA), fluorescein angiograms (FA), and oral fluorescein angiograms were recorded with a confocal scanning laser ophthalmoscope. Software was used to average multiple images from a 10-20 image series (over 0.5-1.0 seconds). Image quality was assessed by two masked observers and graded on a scale of 0-3. A more quantifiable grading method was devised by adding a variable amount of Gaussian noise to the improved image until the original and image averaged image appeared equal. RESULTS: Masked review showed mild to strong improvement of visualisation of structures including borders of CNV. Improvement varied depending on the type and phase of the angiogram. Improvement was highest in late phase FA, mid and late phase ICGA, and all phases of oral FA. CONCLUSION: Image averaging using software based algorithms improves the quality of angiographic images, particularly late ICGA images and oral FAs. This method may assist in the visualisation of choroidal neovascularisation in age related macular degeneration.


Subject(s)
Choroidal Neovascularization/diagnosis , Image Processing, Computer-Assisted/methods , Macular Degeneration/diagnosis , Adult , Aged , Aged, 80 and over , Algorithms , Choroidal Neovascularization/etiology , Coloring Agents , Female , Fluorescein Angiography , Humans , Indocyanine Green , Macular Degeneration/complications , Ophthalmoscopy/methods
16.
J Ocul Pharmacol Ther ; 21(3): 205-9, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15969637

ABSTRACT

OBJECTIVE: We previously reported a long-lasting crystalline lipid pro-drug of cyclic cidofovir, hexadecyloxypropyl-cyclic-cidofovir (HDP-cCDV), to treat experimental retinitis in rabbit eyes. With HDP-cCDV there was a longer intraocular therapeutic effect than with cidofovir (CDV) and no toxicity with 100 microg/eye. It has been known that CDV and related analogues lower intraocular pressure (IOP) after local use, and it is also accepted that the guinea pig is a better model to study this toxicity before human clinical trials. METHODS: HDP-cCDV was intravitreally injected into 10 guinea pig eyes in doses of 4, 9, and 18 microg in 20 microL/eye. An 18-microg quantity is the dose equivalent to 100 microg/eye in the rabbit. Only one eye of each animal received drug and the fellow eye served as the control. After injection, the eyes were monitored with tonometry, ophthalmoscopy, electroretinography (ERG), and histology. RESULTS: Intravitreal injections of doses of 18 microg/eye or lower revealed no toxicity and a high therapeutic index (132,000 to 3300 times higher than the 50% effective concentration for human cytomegalovirus) during 10 weeks of observation. The crystalline drug depot was ophthalmoscopically visible in the inferior vitreous cavity for 5-10 weeks. There was no difference in IOP between the drug-injected and control eyes at any time points (P > 0.05) except for day 3 after drug injection (P = 0.0338). All eyes demonstrated a normal ERG waveform with no differences between the treated and the fellow control eyes (P = 0.85). Histology revealed normal morphology and structures of the retina and ciliary body in all eyes (with or without treatment). CONCLUSION: Crystalline HDP-cCDV may be a long-lasting and safer alternative to cidofovir to treat CMV retinitis without the retinal or ciliary body toxicity observed with CDV.


Subject(s)
Antiviral Agents/toxicity , Ciliary Body/drug effects , Cytosine/analogs & derivatives , Intraocular Pressure/drug effects , Organophosphonates/toxicity , Retina/drug effects , Animals , Ciliary Body/pathology , Cytomegalovirus Retinitis/drug therapy , Cytosine/toxicity , Delayed-Action Preparations , Electroretinography , Guinea Pigs , Injections , Retina/pathology , Vitreous Body/drug effects , Vitreous Body/metabolism
17.
Br J Ophthalmol ; 87(7): 853-5, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12812884

ABSTRACT

BACKGROUND: Healed cytomegalovirus (CMV) retinitis in the setting of highly active antiretroviral therapy (HAART) is complicated by inflammatory sequelae and vision loss. AIM: To determine the long term visual outcome of AIDS patients with CMV retinitis who received HAART. METHODS: 90 eyes of 63 consecutive AIDS patients with extramacular CMV retinitis were studied prospectively. RESULTS: Immune recovery status was related to time to onset of epiretinal membrane (p=0.05) and cystoid macular oedema (p=0.06) as well as to the incidence of cataract (p=0.001) and moderate vision loss (p<0.0001). Severe vision loss was associated with retinal detachment (p<0.001). CONCLUSION: AIDS patients with extramacular CMV retinitis lose vision while on HAART. HAART related immune recovery is associated with increased frequencies of epiretinal membrane, cystoid macular oedema, cataract, and retinal detachment with resultant vision loss in AIDS patients with healed CMV retinitis.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antiretroviral Therapy, Highly Active/methods , Cytomegalovirus Retinitis/drug therapy , Vision Disorders/etiology , AIDS-Related Opportunistic Infections/complications , Adult , Cataract/etiology , Cytomegalovirus Retinitis/complications , Epiretinal Membrane/etiology , Female , Humans , Macular Edema/etiology , Male , Prospective Studies , Retinal Detachment/etiology , Time Factors , Treatment Outcome , Uveitis/etiology
18.
Br J Ophthalmol ; 86(12): 1390-4, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12446372

ABSTRACT

AIMS: To report on the intraindividual and interindividual variability of tumour size (height and base diameter) measurements using standardised echography in a masked prospective study. METHODS: 20 consecutive eyes of 20 patients were examined on four different visits by three experienced examiners using standardised echography. As common in standardised echography, tumour height was evaluated with A-scan technique, while transverse and longitudinal base diameter were calculated with B-scan. RESULTS: Tumour height measurements using A-scan were more accurate than base diameter measurements using B-scan. The standard deviation for tumour height over all visits/measurements was 0.18 mm (A-scan), 0.79 mm for transverse, and 0.69 mm for longitudinal base diameters (B-scan). The interclass correlation coefficient (ICC) was much higher for tumour height measurements with A-scan (0.7735 for three examiners on one visit) than for transverse (0.6563) or longitudinal (0.4522) base diameter measurements with B-scan techniques. CONCLUSIONS: A-scan techniques for tumour height measurements provide very reproducible results with little intraindividual and interobserver variability. As B-scan techniques for tumour base evaluation are less accurate they should be used for topographic and morphological examinations.


Subject(s)
Melanoma/diagnostic imaging , Uveal Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Melanoma/pathology , Middle Aged , Observer Variation , Prospective Studies , Reproducibility of Results , Ultrasonography , Uveal Neoplasms/pathology
19.
Ophthalmologe ; 99(7): 545-8, 2002 Jul.
Article in German | MEDLINE | ID: mdl-12148301

ABSTRACT

INTRODUCTION: The post-irradiation regression rate of uveal melanomas is a prognostically significant factor for the development of metastases. Other predictive factors for metastases are histological networks which are imagable with confocal ICG angiography. The purpose of this study was to evaluate a possible connection of networks in the ICGA and tumor regression rates. METHODS: We compared the post-irradiation regression rates (as %) in 20 patients 1 year after brachytherapy with networks identified in pre-treatment indocyanine green angiography (ICGA). The ICG angiography was performed before irradiation, 10 patients were irradiated with Ru-106 and 10 were irradiated with Id-125. RESULTS: The mean preoperative maximum apical height was 5.2 mm [SD: 1.5 mm; Ru106 group: 5.7 mm (SD: 1.0 mm); Id-125 group: 5.0 mm (SD: 1.9 mm)]. In 11 patients (55%) (Ru-106: 5; Id-125: 6) we found networks in the preoperative ICG. The mean regression rate in tumors with networks was 51.3% (SD: 14.7%) and 28.0% (SD: 16.4%) in the group without networks. The difference between both groups was statistically significant (p = 0.003, Mann-Whitney test). No statistically significant difference in the regression rates was found between the two groups of brachytherapy Ru-106 and Id-125 (p = 0.165, Mann-Whitney test). DISCUSSION: Highly proliferative tumors are known to be more sensitive to irradiation. This may be one reason why tumors with a rapid post-irradiation regression are the more aggressive ones with regard to later development of metastases. Histopathological networks are also known to be a strong indication of more aggressive, metastasizing tumors. These networks are also imagable in ICG angiography. Our observation emphasizes a connection between networks in ICG angiography and regression rates of uveal melanomas after brachytherapy.


Subject(s)
Brachytherapy , Fluorescein Angiography/methods , Melanoma/blood supply , Neovascularization, Pathologic/diagnosis , Uveal Neoplasms/blood supply , Adult , Aged , Aged, 80 and over , Female , Humans , Indocyanine Green , Male , Melanoma/radiotherapy , Microcirculation/radiation effects , Middle Aged , Neovascularization, Pathologic/radiotherapy , Prognosis , Treatment Outcome , Uveal Neoplasms/radiotherapy
20.
Ophthalmologe ; 99(3): 193-9, 2002 Mar.
Article in German | MEDLINE | ID: mdl-11917803

ABSTRACT

BACKGROUND: We have previously shown that histologically described microcirculation patterns (MCP) can be visualized with indocyanine green (ICG) angiography. We have designed a prospective study to evaluate the prognostic value of these angiographically imaged MCP in small choroidal melanocytic lesions. In this report we describe the design of the study, characterize the patient collective, and present the first results. PATIENTS AND METHODS: In this prospective nonrandomized observational study, unilateral choroidal melanocytic lesions with 1.5-5.5 mm maximum apical height are observed until growth is determined according to defined criteria. Variables are demographic parameters, subjective symptoms, subretinal fluid, location and dimension of tumor, hemorrhage, color, orange pigment, and MCP determined by ICG angiography: normal, straight, parallel without crosslinking, parallel with crosslinking, arcs without branching, arcs with branching, loop, and network. RESULTS: Seventy patients (22 males, 48 females; age: 33-88 years, median: 64 years) have been included up to now: 19 tumors showed growth so far (time to growth: 51-946 days, median: 127 days). The following parameters were statistically significantly correlated with time to tumor growth: flashes (p = 0.082), orange pigment (p = 0.012), subretinal fluid (p < 0.001), maximum basal tumor diameter (p = 0.001), maximum apical tumor height (p < 0.001), parallel with crosslinking (p < 0.001), arcs with branching (p = 0.006), loop (p < 0.001), and network (p < 0.001). Of these, complex MCP (parallel with crosslinking, arcs with branching, loop and/or network) showed the strongest correlation with time to tumor growth in a Cox regression model. Based on our data, the positive predictive value of imaging complex MCP (for growth within 12 months) is 78% and the negative predictive value is 98%. CONCLUSION: Our patient collective demonstrates comparable prognostic parameters for time to growth as described in the literature. In addition, the ICG angiographic detection of complex MCP is more strongly predictive of the time to growth than other clinically determinable factors. Thus, we recommend this examination for patients with small choroidal melanocytic lesions, if the patient is to be counseled regarding the likely biologic behavior of his tumor.


Subject(s)
Choroid Neoplasms/diagnosis , Fluorescein Angiography , Melanoma/diagnosis , Adult , Aged , Aged, 80 and over , Female , Humans , Indocyanine Green , Male , Microcirculation , Middle Aged , Prognosis , Prospective Studies , Time Factors
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