Influence of laser photocoagulation for clinically significant diabetic macular oedema (DMO) on short-wavelength and conventional automated perimetry

The aim of the study was to determine the effect of laser photocoagulation for clinically significant diabetic macular oedema (DMO) on macular visual function as assessed by conventional and short-wavelength automated static threshold perimetry. The sample comprised 24 patients who required laser photocoagulation for clinically significant DMO (mean age 59.75 years, range 45-75 years). One eye of each patient was selected for the study. Patients underwent conventional and short-wavelength perimetry using programme 10-2 of the Humphrey Field Analyser on two separate occasions prior to treatment and subsequently within 1 week of, and at 1, 2, 4 and 12 weeks after, treatment. The pointwise pattern deviation plot was analysed for conventional perimetry and a pointwise horizontal and vertical hemifield asymmetry analysis was derived for short-wavelength perimetry (thereby negating the influence of pre-receptoral absorption). The extent of sensitivity loss was determined by counting the number of stimulus locations with statistical probability levels of p less than 0.05. Group mean log minimum angle of resolution (logMAR) visual acuity was largely unchanged over the course of the study. Conventional perimetry showed an increase in the group mean number of abnormal contiguous stimulus locations from 2.4 (SD 4.3, range 0-14) immediately prior to treatment, to 12.4 (SD 7.8, range 0-30) within 1 week of treatment; at 3 months post-treatment, the group mean number of abnormal contiguous stimulus locations was 8.1 (SD 6.5, range 0-20). A similar but less pronounced change was found for short-wavelength perimetry. The spatial position of the post-treatment localised sensitivity loss corresponded with the area of retinal photocoagulation. Despite proven benefit in the stabilisation of visual acuity, laser photocoagulation for clinically significant DMO invariably results in a localised loss of perimetric sensitivity within 10 degrees eccentricity of the fovea. Evidence for the value of laser therapy for clinically significant DMO must be re-examined.     

Retinal hypoxia in long-term diabetic cats

PURPOSE: To determine whether the retina is hypoxic in early stages of diabetic retinopathy in cats and to correlate intraretinal PO2 with fluorescein angiographic and histologic alterations. METHODS: Intraretinal PO2 was measured with microelectrodes in three cats with long-standing diabetes (>6 years) that had been followed with fluorescein angiographs every 6 months. Average PO2 in the inner vascularized half of the retina was compared with similar measurements in 21 control animals. Photoreceptor oxygen consumption was also compared. The retinal vascular endothelium of the diabetic animals was stained for ADPase activity in flatmounts, and transverse sections were used to visualize microscopic alterations in vascular structure. RESULTS: PO2 in the inner half of the retina was abnormally low in the diabetic cats, 7.7+/-5.2 mm Hg (35 penetrations in 3 cats) versus 16.4+/-9.3 mm Hg in normal cats (85 penetrations in 21 cats) (P < 0.001). Oxygenation was almost normal in some regions of the diabetic retinas, but little evidence of oxygen supply from the retinal circulation was observed in other regions. Inner retinal hypoxia was present in areas with no detectable capillary dropout in fluorescein angiograms or flatmounts. The worst changes histologically were microaneurysms, leukocyte and platelet plugging of aneurysms and venules, and degenerating endothelial cells in capillary walls. These histologic abnormalities were confined to small regions, some of which could be positively correlated with markedly abnormal PO2 profiles. Photoreceptor oxygen utilization was not affected in two diabetic cats, but was below normal in one animal in which choroidal PO2 was low. CONCLUSIONS: This is the first direct demonstration of retinal hypoxia in early diabetic retinopathy, before capillary dropout was evident clinically. Hypoxia was correlated with endothelial cell death, leukocyte plugging of vessels, and microaneurysms.     

Erythropoietin in diabetic macular edema and renal insufficiency

Erythropoietin was administered to five anemic azotemic diabetic subjects for 1 year to assess the effect of increasing red cell mass on clinical well-being and the course of renal functional decline. None of the subjects manifested worsened hypertension or cerebrovascular or cardiovascular complications despite an increase in mean hematocrit from a baseline mean of 29.6% to a mean of 39.5%. The serum creatinine concentration after 1 year of treatment with erythropoietin was 3.7 mg/dL, which was unchanged from the baseline value of 3.5 mg/dL. Plasma viscosity remained constant as red cell mass increased. Although the viscosity of whole blood rose as the hematocrit increased, it was within the range of normal blood viscosity for an equivalent hematocrit. The favorable impact of erythropoietin treatment on three diabetic subjects who had macular edema and anemia is described. One hypothesis to explain the benefit of a raised hematocrit on both diabetic nephropathy and retinopathy is that the metabolic, hormonal, and hemodynamic components of the diabetic syndrome, in concert, produce tissue and cellular hypoxia that is ameliorated in part by the greater oxygen-transporting capacity of a raised red cell mass. The pseudohypoxia of diabetes may be implicated in the pathogenesis of diabetic neuropathy, retinopathy, muscular dysfunction, and nephropathy.     

Retinal functions in dominant cystoid macular dystrophy (DCMD)

Dominant cystoid macular dystrophy (DCMD) occurred in 28 members of 5 unrelated families. The disease is characterized by cystoid macular oedema and leakage from retinal capillaries in the posterior pole. Colour vision examination reveals a type I red-green defect with concomitant blue-yellow defectiveness; the latter may be caused by the leaking capillaries. The ERG is normal. The EOG is subnormal. Darkadaptation curves are often slightly disturbed. There are frequently also aspecific pigmentary alterations in the peripheral fundus.     

Vitrectomy for traction macular detachment in diabetic retinopathy

BACKGROUND: A small number of eyes with proliferative diabetic retinopathy develop massive central fibrovascular membranes characterized by vitreoretinal tractions along the arcades and optic disk and retinal traction lines extending through the macula. The aim of our study was first to present the results of vitrectomy for removal of these central membranes and second to determine the correlation between preoperative parameters and postoperative visual outcome. SUBJECTS AND METHODS: We treated 28 eyes with severe central fibrovascular diabetic membranes by a modified bi-manual en bloc excision technique during vitrectomy. Preoperative examination included general status, visual acuity, slit-lamp investigation, binocular funduscopy, ultrasound investigation and visual evoked potentials (VEP). Further, we analyzed intraoperative complications and postoperative anatomic and functional outcomes. RESULTS: The retinas of 27 eyes with central traction retinal detachments were reattached by surgery. With a minimum of 6 months' follow-up, the macula remained attached in 24 eyes, while the retinas were completely attached in 22 eyes. Preoperative visual acuity was defective light perception to 0.1; an increase in visual acuity to maximal 0.1 was seen in 50% of the patients postoperatively. Preoperative visual acuity of light perception was associated with no functional improvement. Preoperative ultrasound investigation gave information about the real anatomic situation of the retina, especially if funduscopy was not possible. The other preoperative parameters could not predict correctly the functional outcome of vitrectomy in diabetics with severe central fibrovascular membranes because of the damage of the optic nerve and the retina. CONCLUSIONS: The high rate of anatomical reattachment after vitrectomy in diabetic eyes with severe central fibrovascular membranes is associated with a slight improvement of function; only preoperative visual acuity of hand motions or better was associated with an improvement of function.     

The study on changes of macular light sensitivity before and after photocoagulation for diabetic macular edema

OBJECTIVE: The study was designed to determine whether laser photocoagulation could damage macular visual function in treatment of diabetic macular edema. METHODS: A prospective clinical trial was taken to determine the effects of argon green (514.5nm) laser photocoagulation on macular light sensitivity (MLS) by comparing the self MLS pairing data collected from a Humphrey automatic visual field analyzer before and after the procedure. Nineteen eyes of 15 patients with diabetic macular edema consistent with its diagnostic criteria were enrolled in this study, a follow-up period being 3 months. RESULTS: The mean MLS at the photocoagulation area, non-photocoagulation area, 5 degrees and 13 degrees eccentricity were significantly decreased within 1 week after the treatment, the drops of MLS were 1.85 dB, 1.05 dB, 0.99 dB, 1.66 dB respectively (P < 0.05). The mean reduction of MLS at the fovea within 1 week after the treatment has no statistical significance. The MLS gradually recovered at the 1st and 3rd month after photocoagulation, and the visual acuities in most of the cases were stable or increased. CONCLUSIONS: MLS is affected little by laser photocoagulation, and photocoagulation can reduce the risk of visual loss or increase visual acuity in an eye with diabetic macular edema.     

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.     

Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone-treated patients

A role for GH in the pathogenesis of diabetic retinopathy has long been postulated. Previous clinical studies, however, have been confounded by hyperglycemia. We have identified 2 cases of retinopathy associated with exogenous GH therapy in nondiabetic patients. Cases were identified through the MedWatch drug surveillance system of the U.S. Food and Drug Administration. Causality by concomitant medications was excluded by a search of the literature and the FDA data base. The first patient, an obese, 31-yr-old male with traumatic hypothalamic injury, presented with nonproliferative retinopathy and macular edema, resulting in decreased visual acuity (OD 20/40-1; OS count fingers), which required laser surgery. Human GH had been initiated at 0.009 mg/ kg.day, 14 months earlier, and titrated to 0.017 mg/kg.day. The second patient, a nonobese, 11-yr-old girl receiving GH for the management of short stature in Turner's Syndrome, presented with neovascularization. GH doses were 0.033 mg/kg.day for the first 17 months and 0.043 mg/ kg.day for the following 5 months. Cumulative laboratory and clinical observations suggest that GH and related peptides have a role in retinal pathology independent of the degree of glucose tolerance.     

Retinal thickness variation in the diabetic patient measured by the retinal thickness analyser

BACKGROUND: Acral melanomas are uncommon. Due to the thick overlying stratum corneum, accurate estimation of margins is difficult for minimally pigmented or amelanotic melanomas on the palm or sole. OBJECTIVE: To describe the use of Mohs micrographic surgery using frozen sections and HMB-45 immunostaining in the treatment of a multiply recurrent acral melanoma that had failed both standard surgery and Mohs surgery. METHODS: The melanoma was excised by Mohs technique, and the margins were checked by frozen section and HMB-45 immunostaining. RESULTS: The melanoma was completely excised in 11 stages, resulting in a defect that covered much of the plantar surfaces of the ball of the left foot, great, second, third, fourth, and fifth toes. No recurrence has been noted in 22 months of follow-up. CONCLUSIONS: HMB-45 immunostaining is a very valuable adjunct to examination of surgical margins for melanoma, particularly when combined with such histologic features as clustering of cells, melanocyte position within the epidermis, and cytologic atypia.     

The effect of acetazolamide on passive and active transport of fluorescein across the blood-retina barrier in retinitis pigmentosa complicated by macular oedema

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide (AZM) reduces macular oedema in some patients with retinitis pigmentosa. To better understand the oedema-reducing effect of AZM, the effect of AZM on passive permeability and active transport of fluorescein across the blood-retina barrier was studied in patients with retinitis pigmentosa and varying degrees of macular oedema. METHOD: The selection of patients was based on an introductory examination including vitreous fluorometry for qualitative assessment of the vitreous. Macular oedema was graded by fluorescein angiographic leakage. The effect of AZM on the transport properties of the blood-retina barrier was determined by differential spectrofluorometry, in a randomised, double-masked, cross-over study, comprising 2 weeks' treatment with AZM (500 mg/day) and 2 weeks' treatment with placebo. The penetration ratio, defined as the ratio between vitreous concentration 3 mm in front of the retina and the plasma integral, was determined for fluorescein and its metabolite fluorescein glucuronide at 30-60 min and at 120 min after fluorescein injection. Passive permeability and unidirectional permeability in the direction vitreous to blood, due to outward active transport of fluorescein, were determined in those cases where the curves for vitreous concentration of fluorescein could be fitted to a mathematical model. Visual acuity was tested by use of ETDRS standard logarithmic charts. RESULTS: Twenty-two patients volunteered to participate in the study. Signs of significant vitreous detachment/liquefaction caused the exclusion of ten patients after the introductory examination. Nine patients with approximately intact vitreous and varying degrees of oedema completed the cross-over study. AZM treatment was related to a decrease in the penetration ratio of 21% for fluorescein (P=0.01) and of 22% for fluorescein glucuronide (P=0.004). Passive permeability and unidirectional permeability were determined in seven patients. AZM caused a decrease of 27% in the passive permeability of fluorescein (from 1.1 x 10(1) nm/s, P=0.031), and a 95% increase in unidirectional permeability of fluorescein (from 1.2 x 10(2) nm/s, P=0.047). AZM led to a reduction in the grade of macular oedema as determined by fluorescein angiography in three out of seven patients. Only small improvements (< or =5 letters) in visual acuity were noted. CONCLUSION: The present study indicates that the oedema-reducing effect of AZM is due to decreased leakage and stimulated active transport across the blood-retina barrier.     

Does wavelength matter when photocoagulating eyes with macular degeneration or diabetic retinopathy?

This article reviews the literature about the safety and benefits of two recombinantly derived proteins, bovine somatotropin (bST) and porcine somatotropin (pST), that likely will be used in animal agriculture in the future. When administered to dairy cows, bST increases milk production per cow approximately 15% to 20% and improves productive efficiency approximately 10%. Administration of pST to growing pigs reduces carcass fat content by as much as 70% to 80% and improves productive efficiency 15% to 35%. Because meat is a major source of total fat and saturated fatty acids in the diets of human beings, pST will allow consumers to include leaner, more nutrient-dense pork in their diets and still meet current dietary guidelines. Although these biotechnologies have not yet received regulatory approval from the Food and Drug Administration (FDA) for commercial use, information published by the FDA, the National Institutes of Health, the US Congress Office of Technology Assessment, and the American Academy of Pediatrics, as well as an extensive body of scientific evidence, indicate that these products are safe for the consumer. Nonetheless, it is important that consumers understand the benefits and safety of these biotechnologies. Dietitians can play an important role in providing information to consumers about the safety and benefits of bST and pST.     

Detection of diabetic macular edema: Nidek 3Dx stereophotography compared with fundus biomicroscopy

PURPOSE: To assess the use of the Nidek 3Dx simultaneous stereophotography camera in diabetic patients, comparing the detection of clinically significant macular edema by fundus biomicroscopy to detection by the Nidek 3Dx simultaneous fundus stereophotograph. METHODS: Two hundred eight eyes of 123 diabetic patients at the Wilmer Retinal Vascular Center were examined for this prospective study between August 1993 and October 1993. Each patient was examined by one of three retina specialists by contact lens biomicroscopy for clinically significant macular edema and foveal center thickening. Nidek 3Dx fundus stereophotographs were obtained and graded independently for clinically significant macular edema and foveal center thickening by a fourth ophthalmologist masked from the clinical examination findings. Percent agreement, kappa statistic, and weighted kappa statistic were determined for the two diagnostic methods. RESULTS: One hundred eighty-four (88%) of the 208 stereophotographs were of sufficient quality to detect clinically significant macular edema; 175 (84%) of the 208 stereophotographs detected foveal center thickening. The agreement between the clinician and the photographic grading, measured by weighted kappa, was 0.52 for clinically significant macular edema and 0.58 for foveal center thickening, representing fair to good agreement beyond chance. Agreement was improved when normal fundus Nidek stereophotographs were available as standards for comparison. CONCLUSIONS: The Nidek 3Dx camera is suitable for photographic detection of clinically significant macular edema and may have a potential advantage over conventional cameras by achieving good-quality, gradable stereophotographs in a large proportion of photographed eyes.     

Volumetric analysis of early macular edema with the Heidelberg Retina Tomograph in diabetic retinopathy

OBJECTIVE: This study describes a new method for the quantification of diabetic macular edema by volumetric analysis with the Heidelberg Retina Tomograph (HRT) scanning laser ophthalmoscope. DESIGN: Topographic images of the macula were obtained in 25 consecutive patients who fitted the inclusion criteria. Twenty age-matched control subjects were randomly selected for a similar examination. PARTICIPANTS: Twenty normal control eyes and 32 eyes of 25 patients with diabetes mellitus were studied. INTERVENTION: Patients with diabetes were examined by HRT and slit-lamp biomicroscopy with a contact lens. On HRT, the volumes above reference plane bound by three consecutive circles centered at the fovea (diameter, 1, 2, and 3 mm) were measured. Measurements were repeated three times in a masked fashion, and the mean measurements were used for the analysis. MAIN OUTCOME MEASURES: Visual acuity, macular edema, and volume above reference plane were measured. RESULTS: There were 19 diabetic eyes with clinical macular edema (deemed positives) and 13 without edema (deemed negatives). Diabetic eyes with macular edema had statistically greater volumes above reference plane than did diabetic eyes without edema (P < 0.001) and greater than the control eyes (P < 0.001) for all three circles. There was no statistically significant difference between volumes measured in eyes without macular edema and control eyes (P = 0.42 for the 1-mm diameter circle; P = 0.72 for the 2-mm diameter circle; and P = 0.19 for the 3-mm diameter circle). For the two smallest circles only, the sensitivity of the HRT was 78.94%, and the specificity was 84.61%. None of the patients missed on the two smallest circles would have been positively identified on the 3-mm diameter circle. CONCLUSION: The HRT can detect and quantify macular edema in diabetes by volumetric analysis with the method the authors have described. It is sufficient to measure the volumes above reference plane of two circles centered on the fovea and measuring 1 and 2 mm in diameter because the 3-mm diameter circle does not increase the system's sensitivity.     

Retinal vessels before and after photocoagulation in diabetic retinopathy. Determining the diameter using digitized color fundus slides

BACKGROUND: Retinal vessel diameter is an important parameter in blood flow analysis. Despite modern digital image technology, most clinical studies investigate diameters subjectively using projected fundus slides or negatives. In the present study we used a technique to examine vessel diameters by digital image analysis of color fundus slides. We investigated in a retrospective manner diameter changes in twenty diabetic patients before and after panretinal laser coagulation. MATERIAL AND METHODS: Color fundus slides were digitized by a new high resolution scanning device. The resulting images consisted in three channels (red, green, blue). Since vessel contrast was the highest in the green channel, we assessed grey value profiles perpendicular to the vessels in the green channel. Diameters were measured at the half-height of the profile. RESULTS: After panretinal laser coagulation, average venous diameter was decreased, whereas arterial diameter remained unchanged. There was no significant relation between the diameter change and the number of laser burns or the presence of neovascularization. CONCLUSIONS: Splitting digitized images into color planes enables objective measurements of retinal diameters in conventional color slides.     

Visual acuity and macular hole size after unsuccessful macular hole closure

We have identified and characterized a novel protein from adult zebrafish retina, which we named ES1. Database search revealed that the ES1 gene has significant similarity to two genes with unknown functions: the Escherichia coli sigma cross-reacting protein 27a (scrp27a) and the human KNP-I/GT335. In situ hybridization and immunohistochemistry experiments showed that both ES1 mRNA and protein are expressed specifically in adult photoreceptor cells. ES1 seems to be a cytoplasmic protein. An ES1-like antigen was also detected in photoreceptor cells of goldfish with anti-ES1 antibodies. The retina specific expression and the evolutionary conservation suggest that ES1 protein may be important for maintaining normal retina structure and function.     

Retinal dystrophies and genetic counselling

Increased patient demand is leading to a corresponding increase in the need for informed genetic counselling in ophthalmic practice which requires refined diagnosis, and a detailed knowledge of molecular genetics. Accurate assessment of risk and visual potential in prospective children is becoming available for a range of retinal dystrophies allowing for more educated decisions to be made by parents.