Variability in photocoagulation treatment of diabetic macular oedema

Purpose: To establish whether differences in the assessment of diabetic macular oedema (DME) with either optical coherence tomography (OCT) or stereoscopic biomicroscopy lead to variability in the photocoagulation treatment of DME. Methods: The differences in the assessment of DME with either OCT or stereoscopic biomicroscopy were analysed by calculating the surface areas and the overlap of retinal thickening. Photocoagulation treatment plans of retinal specialists were compared by evaluating the number and location of planned laser spots. Results: The threshold for and dosage of photocoagulation differ depending upon whether the basis of retinal thickness diagnosis is clinical observation or OCT. The overlap in laser spot location based on the assessment of DME with OCT or biomicroscopy averages 51%. Among retinal specialists, the treatment plans differed in the laser spot count by six‐ to 11‐fold. Conclusion: Diabetic macular oedema photocoagulation treatment threshold and dosage of laser spots differ depending on whether thickness assessments are based on stereoscopic slit‐lamp biomicroscopy or OCT. In addition, retinal specialists differed in the number and placement of planned laser spots even when given identical information concerning DME and treatable lesions. This variability in the photocoagulation treatment of DME could lead to differences in patient outcome and laser study results.     

Vitrectomy for cystoid macular oedema with attached posterior hyaloid membrane in patients with diabetes

AIM: To report the success of vitrectomy in eliminating cystoid macular oedema and improving vision in three eyes of two patients with diabetic cystoid macular oedema. In all of the eyes there was no ophthalmoscopic evidence of traction from a posterior hyaloid membrane or from proliferative tissue. METHODS: Pars plana vitrectomy was performed on three eyes of two patients with diabetic cystoid macular oedema who did not show traction upon examination with a slit lamp biomicroscope and a scanning laser ophthalmoscope. RESULTS: Cystoid changes disappeared 1, 3, and 5 days, postoperatively, and diffuse macular oedema resolved within 2 weeks. The visual acuity was improved and maintained. CONCLUSION: Vitrectomy can be effective in some patients with diabetic cystoid macular oedema even in patients who lack evidence of traction by ophthalmoscopy.     

Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema

Purpose: To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO). Methods: Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit‐lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2–4, 8 and 12 weeks post‐injection. Best corrected VA and CRT were analysed in both groups. Results: In the non‐pretreated group, mean BCVA improved from 0.76 ± 0.33 (baseline) to 0.57 ± 0.30 and 0.54 ± 0.27 at 2–4 weeks and 8 weeks post‐injection, respectively (p = 0.02, p = 0.014, paired t‐test). Mean CRT decreased from 632.4 ± 196.0 μm (baseline) to 392.3 ± 113.6 μm and 370.4 ± 141.7 μm at the same time‐points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 ± 0.30 (baseline) to 0.53 ± 0.33 at 2–4 weeks post‐injection (p = 0.01), and mean CRT decreased from 583.9 ± 180.7 μm (baseline) to 404.1 ± 197.9 μm at 2–4 weeks post‐injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post‐injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side‐effects developed during follow‐up. Conclusions: One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.     

Two-wavelength fundus autofluorescence and macular pigment optical density imaging in diabetic macular oedema

Purpose

To evaluate the application of 488 and 514 nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features.

Patients and Methods

A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514 nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference.

Results

Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488 nm FAF, 0.63 for 514 nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488 nm FAF; 55.2 and 94.8% for 514 nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488 nm FAF and MPOD imaging, DMO was better visualised in comparison with 514 nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts.

Conclusion

MPOD imaging, and particularly its combination with 488 nm and 514 nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula.     

United Kingdom National Ophthalmology Database Study: Diabetic Retinopathy; Report 1: prevalence of centre-involving diabetic macular oedema and other grades of maculopathy and retinopathy in hospital eye services

Aims

To report estimates of the prevalence of diabetic retinopathy (DR) and maculopathy grades for a large cohort of patients managed by the UK hospital eye service (HES).

Methods

Anonymised data were extracted from 30 UK NHS hospital trusts using a single ophthalmic electronic medical record (EMR) for the period from April 2000 to November 2010 to create the National Ophthalmology Database (NOD). From 2007, the EMR facilitated capture of a nationally agreed-upon standardised data set (DR Structured Assessment) relating to the presence or absence of clinical signs of DR and maculopathy. An algorithm in the software automatically calculated the Early Treatment of Diabetic Retinopathy Study grades of retinopathy and maculopathy.

Results

Between 2007 and 2010, 307 538 patients had data on the NOD, with 76 127 (24.8%) patients having been recorded as having diabetes. The proportion of patients with diabetes who had a structured assessment increased from 50.7% (2007) to 86.8% (2010). In each NHS year, 12.6–20.6% of eyes with structured assessments had no DR; 59.6–67.3% had non-proliferative DR; and 18.3–20.9% had active or regressed proliferative DR. Clinically significant macular oedema was present in 15.8–18.1% of eyes, and in 8.7–10.0% of eyes, this involved the central macula.

Conclusion

This study provides contemporary estimates of the prevalence of retinopathy and maculopathy grades in a large cohort of patients with diabetes managed by the UK HES. Centre-involving diabetic macular oedema, potentially amenable to anti-VEGF therapy, is present in the eyes of almost 10% of these patients. This information is useful for clinicians, health-care economists, and commissioners involved in planning and delivering diabetic eye services.     

Local retinal sensitivity in relation to specific retinopathy lesions in diabetic macular oedema

Purpose: To study microperimetric macular sensitivity in diabetic macular oedema (DMO) in relation to lesion characteristics obtained by optical coherence tomography (OCT), colour fundus photography, and fluorescein angiography (FA). Methods: The study comprised 20 eyes in 15 patients with nonproliferative diabetic retinopathy and recently diagnosed untreated DMO. Investigations included microperimetry, fluorescein angiography, colour fundus photography, and OCT. All measures and gradings were made for each of the nine fields of an early treatment diabetic retinopathy study macula template. Statistical analysis was made using Spearman’s nonparametric test including field and mean values within fields. Comparisons were made within the study population and with a normative microperimetry database. Results: Subnormal microperimetric sensitivity was associated with cystoid macular oedema, both in foveal petaloid (r = ?0.50, p = 0.02) and extrafoveal honeycomb patterns (r = ?0.8, p < 0.0001) and with outer nuclear layer cysts (r = ?0. 5, p = 0.024), inner nuclear layer cysts (r = ?0.31, p = 0.03), and hard exudate (r = ?0.38, p = 0.0026). There was no detectable effect of focal noncystoid oedema (r = ?0.16, p = 0. 48), diffuse noncystoid oedema (r = ?0.14, p = 0.55), capillary nonperfusion (r = ?0.33, p = 0.15), intraretinal haemorrhage (r = ?0.15, p = 0.53), or serous retinal detachment (r = ?0.11, p = 0.63). Foveal thickening was associated with locally reduced sensitivity (r = ?0.54, p = 0.01). Foveal sensitivity was positively correlated to the visual acuity, with a correlation of 0.44 and a borderline significance (p = 0.0509). Conclusions: Macular hard exudates and cystoid oedema were associated with locally reduced sensitivity. Thus, the lesions associated with reduced sensitivity for a white‐on‐white stimulus were such lesions that cause light to be blocked or scattered before it reaches the photoreceptors, suggesting that optical effects are a major cause of sensitivity loss.     

Contrast sensitivity following focal laser photocoagulation in clinically significant macular oedema due to diabetic retinopathy

Purpose : To evaluate the influence of focal laser photocoagulation on contrast sensitivity in diabetic patients with clinically significant macular oedema (CSMO). Methods : A prospective non‐comparative interventional study was performed on a group of patients with CSMO at Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, a tertiary eye care centre. Thirteen diabetic patients (14 eyes) with CSMO and no history of prior photocoagulation were recruited for this study. Direct focal photocoagulation of all leaking microaneurysms was performed using an argon green laser (514 nm). A contact lens was used as a slit lamp delivery system. Evaluation of the best corrected Snellen visual acuity, contrast sensitivity, slit lamp biomicroscopy, macular status on direct ophthalmoscopy and fluorescein angiography was carried out 1 month and 3 months after laser photocoagulation. Results : Following direct focal laser photocoagulation, focal CSMO resolved completely in all but one eye, 4–8 weeks later, as seen on slit lamp biomicroscopy and/or fluorescein angiography. Post‐treatment, visual acuity remained stationary in eight eyes, improved by one line in three eyes, by two lines in two eyes and by three lines in one eye. The mean ± SD pretreatment and post‐treatment decimal visual acuities were 0.49 ± 0.30 and 0.59 ± 0.28, respectively. The mean ± SD pre‐laser contrast sensitivity score was 121.3 ± 83.6, which increased significantly to a mean ± SD of 151.6 ± 80.5 following direct focal photocoagulation. Conclusion : Focal argon laser photocoagulation in CSMO in diabetics helps in improving the contrast sensitivity and stabilizes the visual acuity. The changes in contrast sensitivity and visual acuity are independent of each other.     

The management of diabetic macular oedema

Diabetic macular oedema (DMO) is a significant cause of visual loss in the working population. Focal/grid photocoagulation remains an effective treatment for DMO and the benchmark to which clinicians compare other newer treatment modalities. There are, however, patients who do not respond adequately or who are refractory to laser photocoagulation. This has led to the development of newer treatments such as the intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors as well as intravitreal corticosteroid releasing delivery systems. Cataract formation and raised intraocular pressure remain the major disadvantages of corticosteroid use. There is mounting evidence that intravitreal VEGF inhibitors with or without combined laser photocoagulation will become the gold standard treatment for DMO.     

Refractive changes after intravitreal ranibizumab injections for diabetic macular oedema

Purpose

The purpose of this study was to evaluate refractive changes after intravitreal ranibizumab injections for the treatment of diabetic macular oedema.

Methods

Participants in this retrospective study were 35 patients (35 eyes) with diabetic macular oedema, who received intravitreal ranibizumab injections. Spherical equivalent refractive power was evaluated before treatment and at least one month after the last injection where no fluid existed. Demographic characteristics, visual acuity, central retinal thickness and the number of injections were recorded and analysed.

Results

The spherical equivalent refractive power did not differ significantly pre‐ or post‐injections. Changes in visual acuity and central retinal thickness were statistically significant before and after injections.

Conclusions

Intravitreal ranibizumab injections did not seem to affect the refractive power of patients with diabetic macular oedema. Therefore, appropriate spectacle correction can be prescribed any time during ongoing treatment with ranibizumab injections.

     

Viewing the choroid: where we stand,challenges and contradictions in diabetic retinopathy and diabetic macular oedema

Diabetic macular oedema (DMO) is the leading cause of vision loss in the working‐age population. Blood–retinal barrier (BRB) dysfunction in diabetic retinopathy (DR), mainly at the level of the retinal vessels, has long been related with leakage and fluid accumulation, leading to macular oedema. However, the nourishment of the macula is provided by the choroid and a diabetic choroidopathy has been described. Therefore, there has been a growing interest in studying the role of the choroid in the pathophysiology of DR and DMO, mainly by optical coherence tomography (OCT). Nevertheless, there are conflicting results in the different studies. We summarize the results from the available studies, describe the limitations and confounding factors and discuss future procedures to avoid bias.     

Five-year visual outcome following laser photocoagulation of diabetic macular oedema

Objective

To evaluate the 5-year visual outcome associated with laser photocoagulation treatment of diabetic macular oedema (DMO), and to investigate the relationship between systemic factors and visual outcomes in a real-life setting.

Methods

The mean annual visual outcomes and systemic parameters of 100 consecutive subjects with type 2 diabetes who underwent the first session of focal/grid macular laser photocoagulation for clinically significant macular oedema between 2003 and 2004 were collected retrospectively and compared with the outcomes of the laser arm of the Diabetic Retinopathy Clinical Research Network (DRCRN trial comparing intravitreal triamcinolone acetonide injection with laser photocoagulation treatment for DMO). The primary outcome measures included the mean change in visual acuity (VA) in 5 years and the influence of systemic factors on final visual outcome.

Results

The mean change in VA at 5 years was −5.23 in a real-life setting for an inner city population. The 3-year outcome was inferior to the clinical trial results with more people gaining vision (≥15 letter gain) in the DRCRN group compared with this cohort (26 vs9%). Furthermore, three times more patients lost vision (>15 letter loss) in the real-life setting of this cohort compared with the clinical trial results of the DRCRN group (27 vs8%, respectively).

Conclusions

The visual outcomes and the control of systemic factors of patients with DMO in this cohort were inferior to those recruited for the clinical trial involving the DRCRN group.     

Diabetic macular oedema and visual loss: relationship to location,severity and duration

Purpose: To assess the relationship between visual acuity (VA) and diabetic macular oedema (DMO) in relation to the location of retinal thickening and the severity and duration of central macular thickening. Methods: Data from 584 eyes in 340 placebo‐treated patients in the 3‐years‐long Protein Kinase C Diabetic Retinopathy Study (PKC‐DRS2) trial were used to investigate the relationship between VA and DMO. Eligible eyes had moderately severe to very severe non‐proliferative diabetic retinopathy and VA of at least 45 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) charts (Snellen equivalent = 20/125). Diabetic retinopathy and DMO status were assessed using stereo photographs. Results: Nearly one third of study eyes had foveal centre‐involving DMO at the start of the trial. Sustained moderate visual loss was found in 36 eyes, most commonly associated with DMO at the centre of the fovea in 73% of eyes. There was a strong relationship (p < 0.001) between foveal centre involvement with DMO and mean VA. Mean VA decreased with increasing retinal thickness at the centre (p < 0.001) and increasing duration of centre‐involving DMO (p < 0.001). Conclusion: This study documents the relationship between duration of DMO and progressive vision loss, and the key role of central foveal involvement in patients with diabetic retinopathy. These data will help to develop future strategies to prevent vision loss.     

Quantitative assessment of macular thickness in normal subjects and patients with diabetic retinopathy by scanning retinal thickness analyser

AIMS: To evaluate the scanning retinal thickness analyser (RTA), a novel non-invasive imaging instrument, in diagnosing and quantitatively characterising diabetic macular oedema, and to investigate the relation between central macula thickness measured by RTA and other clinical examinations. METHODS: Central macular thickness was measured using the RTA in 40 normal subjects and 60 patients with diabetic retinopathy. The reproducibility of the retinal thickness measurements was evaluated by calculating the mean of the inter- and intrasession variations. Central macular thickness was correlated with the results of visual acuity measurements, biomicroscopy, and fluorescein angiography. RESULTS: Intra- and intersession reproducibility of the RTA in normal subjects was plus or minus 5.2% (16 microns) and plus or minus 6.1% (19 microns), respectively. The mean central macular thickness was 182 (SD 16) microns in normal subjects, 283 (116) microns in diabetic eyes without clinically significant macular oedema (CSMO), and 564 (168) microns in diabetic eyes with CSMO. Central macular thickness was significantly greater (p < 0.001) in eyes with diabetic retinopathy than in normal subjects, even when macular thickening did not meet the standard for CSMO (p = 0.019) measured by biomicroscopy. Although greater fluorescein leakage at the macula results in greater central macular thickness, only eyes with diffuse leakage had statistically significant macular thickening compared with normal subjects (p = 0.022). Central macular thickness measured with the RTA was significantly correlated with the logarithmic converted visual acuity (r2 = 0.76) in diabetic eyes. CONCLUSION: Scanning RTA, which has good reproducibility, might be useful to quantitatively detect and monitor macular thickening in diabetic retinopathy. Central macular thickness was highly correlated with logarithmic converted visual acuity in diabetic macular oedema.     

The RELATION study: efficacy and safety of ranibizumab combined with laser photocoagulation treatment versus laser monotherapy in NPDR and PDR patients with diabetic macular oedema

Purpose

To assess efficacy and safety of intravitreal ranibizumab 0.5 mg plus laser (COMBI) versus laser monotherapy (LASER) in patients with visual impairment due to diabetic macular oedema (DME) in either nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) and to analyse the relevance of inner versus outer retinal thickness.

Methods

In this double‐masked, multicentre phase IIIb study, patients (N = 128) were randomized (2:1) to receive COMBI (n = 85) versus LASER (n = 43). Patients received four initial monthly injections of ranibizumab 0.5 mg (COMBI) or sham (LASER) followed by pro re nata (PRN) injections. In both groups, patients received laser at baseline and additional laser at 3 monthly intervals, as needed. The study was started in 2010 and was prematurely terminated due to approval of ranibizumab for DME.

Results

The least squares (LS) mean change in mean best‐corrected visual acuity (BCVA) from baseline to month 12 was higher in the COMBI (6.5) versus LASER (2.3) group (LS mean difference: 4.2 [95% CI 0.9; 7.4] letters, p = 0.01, primary end‐point). There was also a tendency in the same direction for the subgroup of 26 patients with PDR (LS mean difference 14.7, p = 0.11). Mean central retinal thickness decreased by 107.3 μm in the COMBI group and by 80.3 μm in the LASER group from baseline to month 12 (p = 0.28). Ranibizumab was well tolerated.

Conclusion

This study showed that ranibizumab plus laser is a valuable treatment option for the management of DME. Patients with DME in PDR might also benefit from combined therapy compared to laser alone.