|Year : 2017 | Volume
| Issue : 2 | Page : 123-130
Retina spotlight: Diabetic retinopathy - Preferred practice patterns
Syed Asghar Hussain1, S Natarajan2, N Kasinathan3, Amjad Salman4, Nazimul Hussain5
1 Department of Ophthalmology, Saveetha Medical College and Hospital, Saveetha University, Chennai, Tamil Nadu, India
2 Chairman and MD, Aditya Jyot Eye Hospital, Mumbai, Maharashtra, India
3 Retina and Vision Care; Retina Service, Dr. Agarwal's Eye Hospitals; Department of Ophthalmology, Hindu Mission Hospital, Chennai, Tamil Nadu, India
4 Vitreoretinal Services, Institute of Ophthalmology, Joseph Eye Hospital, Trichy, Tamil Nadu, India
5 Aditya Jyot Institute of Vision Science and Research; Department of Ophthalmology, Al-Zahra Pvt. Hospital, Sharjah, UAE
|Date of Web Publication||26-Dec-2017|
Aditya Jyot Institute of Vision Science and Research; Department of Ophthalmology, Al-Zahra Pvt. Hospital, Sharjah
Dr. Syed Asghar Hussain
Department of Ophthalmology, Saveetha Medical College and Hospital, Saveetha Nagar, Thandalam, Chennai - 602 105, Tamil Nadu
Source of Support: None, Conflict of Interest: None
The management of diabetic retinopathy (DR) has always been a right combination of medical and surgical interventions, influenced by various landmark international clinical trials and treatment guidelines as proposed by various bodies such as the American Academy of Ophthalmology, the Royal College of Ophthalmologists, the International Council of Ophthalmology, and the All India Ophthalmological Society to name a few. This article aims to share the various best practices, presently being followed by senior vitreoretinal surgeons, both nationally and internationally, in managing DR, as we are experiencing a paradigm shift in the investigative modalities and treatment regimens, as compared to those which were followed, just a decade ago. A literature search was conducted using the various keywords, for the years 1980–2017 that included pertinent information from the review of more than 3537 citations collectively, using PubMed, Medline, and Hinari databases, which included comprehensive and systematic literature review and meta-analysis reports. Articles were included, only if they contributed new information about the treatment of DR, techniques in widespread clinical use and excluded those related to techniques that are considered experimental and redundant. Studies with follow-up of <18 months were excluded from this review. The relevant articles were thoroughly analyzed, with each being rated, based on the strength of the study design and weight of evidence.
Keywords: Diabetic retinopathy, diabetic macular edema, proliferative diabetic retinopathy, ETDRS, DCCT, DRS, Epidemiology of Diabetes Interventions and Control, United Kingdom Prospective Diabetes Study, DRCR.net, Ranibizumab (Lucentis®, Genentech), Bevacizumab (Avastin®, Roche, Genentech), Aflibercept (Eylea®, Regeneron Therapeutics), Triamcinolone acetonide, Pan retinal photocoagulation
|How to cite this article:|
Hussain SA, Natarajan S, Kasinathan N, Salman A, Hussain N. Retina spotlight: Diabetic retinopathy - Preferred practice patterns. TNOA J Ophthalmic Sci Res 2017;55:123-30
|How to cite this URL:|
Hussain SA, Natarajan S, Kasinathan N, Salman A, Hussain N. Retina spotlight: Diabetic retinopathy - Preferred practice patterns. TNOA J Ophthalmic Sci Res [serial online] 2017 [cited 2019 Dec 11];55:123-30. Available from: http://www.tnoajosr.com/text.asp?2017/55/2/123/221441
| Introduction|| |
It is very disheartening to know that India is set to emerge as the diabetic capital of the world. The World Health Organization (WHO) has estimated that by the year 2030, India will have 79.4 million diabetics; the largest number of diabetics in any nation in the world; steadily increasing from a mere 31.7 million people affected by diabetes mellitus (DM), in the year 2000. According to the WHO, almost all people affected by type 1 DM and around two-thirds of those affected by type 2 DM, are estimated to develop diabetic retinopathy (DR). The management of DR involves a right combination of medical and surgical interventions, guided by various landmark international clinical trials and treatment guidelines.
| Literature Search|| |
A literature search was conducted using the various keywords, for the years 1980–2017 that included pertinent information from the review of more than 3537 citations collectively, using PubMed, Medline, and Hinari databases, which included a comprehensive and systematic literature review and meta-analysis reports. Articles were included, only if they contributed new information about the treatment of DR, techniques in widespread clinical use and excluded those related to techniques that are considered experimental and redundant. Studies with follow-up of <18 months were excluded. The relevant articles were thoroughly analyzed, with each being rated, based on the strength of the study design and weight of evidence.
| What are the Indications for Laser Photocoagulation in Diabetic Retinopathy? What are the Practical Tips That One Should Follow While Planning Panretinal Photocoagulation?|| |
Dr. S. Natarajan:Laser photocoagulation should be considered in proliferative DR (PDR) with or without vitreous hemorrhage (VH), new vessels on the disc, vitreoretinal traction, rubeosis iridis, and neovascular Glaucoma. Furthermore, Supplemental panretinal photocoagulation (PRP) is indicated for unstable DR with new vessels elsewhere (NVEs) or VH or subhyaloid hemorrhage. The focal laser is advocated for extrafoveal leaking microaneurysms causing clinically significant macular edema (CSME). All patients with severe non-PDR (NPDR) can be observed with good patient education.
Dr. N. Kasinathan: In cases of PDR, around 2-3 sittings of PRP (and “Fill In PRP”, wherever required), is recommended. One should look for CSME, circinate retinopathy, and macular edema <300 microns without neurosensory detachment. Practical tips for macular lasers would entail a detailed informed consent from the patient. The procedure should be clearly explained to the patient in advance and hence that unnecessary eye movements can be avoided. One should use good topical anesthesia and a coupling gel. One should also ensure a clear media; spot size 100 microns, single pulse, and power <150 Mw. Every retinal specialist should know the laser lens magnification factor. Practical tips for PRP would entail, ensuring a clear media, spot size 300 microns, 200–300 ms pulse interval, power 200–400 maw, and based on media haze. Practical tips for fill-in PRP would entail a preference toward laser indirect ophthalmoscope delivery. The burn intensity for macular laser should be mild burns or faint whitening, and for PRP laser-moderate intensity, burns are to be applied.
Dr. Amjad Salman: Laser is still immensely useful in the management of diabetic macular edema (DME). It has 2 main roles. As a primary treatment, in cases of noncenter involving DME, the laser is still the preferred modality of treatment. Focal laser to parafoveal areas of leakage is very effective in preventing visual loss due to DME. It is also used as an adjunct to intravitreal anti-vascular endothelial growth factor (VEGF) drugs in center-involving DME that responds partially or inadequately to anti-VEGF therapy. The laser can be planned 6 weeks to 3 months after anti-VEGF therapy helps to reduce macular edema as well as to reduce the number of repeat injections required. Although studies have shown the efficacy of anti-VEGF injections alone in managing DME, in the Indian context, patient acceptance for multiple injections is limited, and laser can help reduce the frequency and number of injections required. The adjunct laser gives best results when macular edema has decreased following anti-VEGF therapy. It is important to remember that laser does not improve vision but reduces the risk of moderate visual loss by 50%. In both situations, laser burns are applied to focal areas of leakage 500–3000 μ from the center of FAZ, areas of retinal thickening, CNP areas with thickening within 3000 μ and areas of diffuse leakage. Burns can be applied in a focal or grid patterns. In cases of repeat laser, areas within 300 μ of FAZ can be considered for treatment.
Dr. Nazimul Hussain: The primary indication for laser in DR is very severe NPDR and PDR with or without high-risk characteristics. However, the scatter laser in PDR may be modified, especially if there is active, large neovascularization (NVZ) either on the disk or elsewhere, which may be suspected to bleed the following laser. Intravitreal injection of Aflibercept (Eylea ®, Regeneron Therapeutics) or Ranibizumab (Lucentis ®, Genentech) before scatter laser is recommended, to regress the new vessels, and to avoid postlaser bleed or potential traction. In treatment naïve DME, the first-line treatment is an intravitreal injection of anti-VEGF until the macula is dry. Often based on a topographic map of optical coherence tomography (OCT) and recurrence of DME inspite of anti-VEGF, the extrafoveal DME is treated with laser and continued with anti-VEGF to get the maximal benefit of treatment. This is applicable only to centre involving DME.
| Concluding Remarks (Dr. syed Asghar Hussain)|| |
PRP still remains the gold standard treatment for preventing visual loss in PDR despite the promise of anti VEGFs, with the former having been accepted as a long-lasting and effective method of reducing pathologic VEGF levels in PDR. It is advocated in noncenter involving DME and as an adjunct to anti-VEGF therapy. The ETDRS has reported that focal PRP reduced the 3-year risk of severe visual loss by 50% in eyes with CSME. However, anti-VEGFs continue to be a very important adjunctive treatment modality to laser.
Which Anti-Vascular Endothelial Growth Factor Should One Choose Bevacizumab (Avastin ®, Roche, Genentech) Versus Ranibizumab (Lucentis ®, Genentech) Versus Aflibercept (Eylea ®, Regeneron Therapeutics)? and When Should One Inject?
Dr. S. Natarajan Ranibizumab (Lucentis ®, Genentech) has about 25 times more affinity for VEGF than Bevacizumab (Avastin ®, Roche, Genentech), whereas Aflibercept (Eylea ®, Regeneron Therapeutics) has about 100 times more affinity for VEGF than Bevacizumab (Avastin ®, Roche, Genentech). Hence, Ranibizumab (Lucentis ®, Genentech) and Aflibercept (Eylea ®, Regeneron Therapeutics) are preferred over Bevacizumab (Avastin ®, Roche, Genentech) for the treatment of center involving DME. Aflibercept (Eylea ®, Regeneron Therapeutics) has a longer half-life enabling every 2-monthly dosing as compared to monthly dosing of Ranibizumab (Lucentis ®, Genentech). As per DRCR.net, eyes with vision 20/50 or less have a greater improvement with Aflibercept (Eylea ®, Regeneron Therapeutics) than Ranibizumab (Lucentis ®, Genentech). Those eyes with better vision than 20/50 have comparable improvements with either Ranibizumab (Lucentis ®, Genentech) or Aflibercept (Eylea ®, Regeneron Therapeutics) and hence either can be used. In our practice, Aflibercept (Eylea ®, Regeneron Therapeutics) is preferred for the above reasons. For center involving DME, Anti-VEGF injections are preferred over intravitreal steroids in the following cases; (a) Young and phakic individuals, (b) Glaucoma suspects, established cases or those having known intraocular pressure (IOP) spikes, and (c) Treatment naïve DME. In general, 3–5 loading doses of anti-VEGF injections are given at monthly or 6-weekly intervals, and further monthly to 3-monthly follow-ups are advised where an increase in macular edema or cystoid spaces would require additional injections. It is worthwhile to note that if the patient is asymptomatic after the previous injection with resolved macular edema and with very few cystoid spaces but not at the fovea, in addition to the foveal contour being maintained, then further injections can be withheld subject to a monthly to 3-monthly follow-up.
Dr. N. Kasinathan: Patients' affordability largely decides the choice of anti-VEGF. In selective cases, before surgery, one should look for flat florid neovascular proliferation, vascular tractional retinal detachment, re-bleeds, and fresh bleeds, and one can visualize most of the retina and sure about the absence of TRD, well-ablated retina and still active NVZ. A definite indication is the presence of NVZ of Iris and Neovascular Glaucoma. Other indications for anti-VEGF are macular edema more than 300 microns, neurosensory detachment, diffuse spongiform macular edema, and PDR with CSME. Practical tips: Informed consent should be taken, adequate blood sugar control, one should avoid injection when there is associated, tractional retinal detachment. Usually, the temporal quadrant is preferred, with the injection being 3.0–4.0 mm away from limbus depending on lens status. One should ensure preoperative usage of Povidone–Iodine eye drops and a sterile atmosphere of an operation theater. Follow-up visits are to be accompanied by serial OCT scans.
Dr. Amjad Salman: Intravitreal anti-VEGF is the preferred method of treatment for all centre-involving DME with mild to moderate visual loss. We consider intravitreal anti-VEGF even in eyes with Snellens 6/9 visual acuity rather than waiting for permanent structural damage to result from long standing macular edema. Anti-VEGF injections are best given as monthly injections for 3 months (loading dose) followed by PRN (“Pro Re Nata” or “as needed”) basis. Bevacizumab (Avastin ®, Roche, Genentech), Ranibizumab (Lucentis ®, Genentech), and Aflibercept (Eylea ®, Regeneron Therapeutics) give equivalent results, except in eyes with visual acuity of 6/24 or less where studies have shown superiority of Aflibercept (Eylea ®, Regeneron Therapeutics). In centers injecting large number of patients, Bevacizumab (Avastin ®, Roche, Genentech) is economical and often the drug of choice. In centers with lower volume, Ranibizumab (Lucentis ®/Accentrix ®, Genentech) is preferred as it comes in a single-use vial with lower risk of contamination. Switching to an alternate anti-VEGF may be considered if therapy with one drug has produced <10% reduction from baseline, in central foveal thickness (CFT), after at least two doses.
Dr. Nazimul Hussain: Bevacizumab (Avastin ®, Roche, Genentech) is not commonly used, due to restrictions for use of non-FDA approved drugs. However, practically Aflibercept (Eylea ®, Regeneron Therapeutics) and Ranibizumab (Lucentis ®, Genentech) work equally in the treatment of DME. Theoretically, it may be possible that Aflibercept (Eylea ®, Regeneron Therapeutics) works a couple of weeks longer than Ranibizumab (Lucentis ®, Genentech). Studies have also recently shown in DRCR.net Protocol T that 2-year data do not show any difference in the outcome. Usually, use both the pharmacological agents can be used equally, but sometimes Aflibercept (Eylea®, Regeneron Therapeutics) has shown better results in more in thickened DME. We need to analyze our own data to see the differences in our ethnic population, the outcome of both in different situations of DME. However, they would not be much different even though slight differences may exist.
| Concluding Remarks (Dr. syed Asghar Hussain)|| |
The pro-angiogenic cytokine VEGF is considered the primary factor involved in NVZ in PDR. The various anti-VEGFs commonly used today are Bevacizumab (Avastin ®, Roche, Genentech), Ranibizumab (Lucentis ®, Genentech) and Aflibercept (Eylea ®, Regeneron Therapeutics). The use of anti-VEGFs in PDR is still an ever changing field, with indications being: (a) Before vitrectomy (not more than 1 week) due to VH (b) Anterior segment NVZ, in patients with an open angle (c) DME with PDR (d) As an adjunct to PRP. Numerous large-scale clinical trials have shown the benefits of anti-VEGF agents in the treatment of DME (viz., DRCR. Net, BOLT and PACORES studies using Bevacizumab (Avastin®, Roche, Genentech); the READ 2, RESTORE, RISE, RIDE, RESOLVE, and DRCR.net studies using Ranibizumab (Lucentis®, Genentech); and the DAVINCI trial using Aflibercept (Eylea®, Regeneron Therapeutics).,,
The Cochrane review on anti-VEGF for prevention of postoperative vitreous cavity hemorrhage (POVCH) after vitrectomy for PDR, has shown that the incidence of POVCH is greatly reduced with anti-VEGFs before vitrectomy, apart from improved best-corrected visual acuity (BCVA), reduced number of instrument exchanges, number and severity of intraoperative bleeds, dissection techniques, and intra-operative retinal tears. Anti-VEGFs before PRP, in patients with DME have shown to reduce the risk of short-term exacerbation of macular edema and associated visual acuity loss.
| Intravitreal Corticosteroids - What to Choose? [Triamcinolone Acetonide Vs. Dexamethasone Implant Ozurdex (Allergan Inc., Usa) Vs. Flucinolone Acetonide Implant (Iluvien, Alimera Sciences, Inc.)]|| |
Dr. S. Natarajan: Intravitreal triamcinolone acetonide (IVTA) and Dexamethasone intravitreal implant (Ozurdex ® [Allergan, Inc., USA]) and Fluocinolone acetonide implant (Iluvien ®, Alimera Sciences) are steroidal agents used for DME. They provide a quicker resolution of macular edema; however, they come with their well-known side-effects. Cataract formation/progression and steroid-induced glaucoma are the most important disadvantages. IVTA has approximately 90% risk of cataract progression and steroid-induced glaucoma, whereas the risk with dexamethasone is lesser, but still significant.,, In addition, Ozurdex ® (Allergan, Inc., USA) implant acts for a longer period as compared to IVTA. Hence, except for economic reasons, Ozurdex ® (Allergan, Inc., USA) would remain the steroidal agent of choice whenever indicated. Intravitreal steroids are not the first-line of treatment for DME. However, they can complement anti-VEGF and lasers in certain situations: (a) Pseudophakic individuals with macular edema with no suspicion of glaucoma, (b) Anti-VEGF injections having a suboptimal response, and (c) In patients who can regularly follow-up for raised IOP or steroid induced glaucoma.
Dr. N. Kasinathan: Affordability decides the choice between Triamcinolone acetonide, Dexamethasone implant Ozurdex ® (Allergan, Inc., USA) and Fluocinolone acetonide implant (Iluvien ®, Alimera Sciences). I personally prefer IVTA rather than subtenons injection. Practical Tips: Informed consent should be taken, indicated in refractory DME, recent stroke/myocardial infarction (MI), postvitrectomized eyes, pregnancy.
Dr. Amjad Salman: Three intravitreal steroids are available for management of DME: Triamcinolone acetonide, Dexamethasone implant (Ozurdex ® [Allergan, Inc., USA]) and Fluocinolone acetonide implant (Iluvien ®, Alimera Sciences)., In India, the choice is often between Ozurdex ® (Allergan, Inc., USA) and Triamcinolone acetonide. Ozurdex ® (Allergan, Inc., USA) has lower propensity to increase IOP and produce cataract than Triamcinolone acetonide; but the risks are still present. These drugs may be considered as first-line therapy in patients who are pseudophakic and not steroid responders; but we prefer to use them in patients who have shown poor response to intravitreal anti-VEGF therapy or where frequent injections are less desirable. It is our clinical experience that intravitreal steroids are more effective in DME with subfoveal serous fluid. However, definitive evidence for this is lacking.
Dr. Nazimul Hussain: My preferred intravitreal steroid is the Dexamethasone implant [Ozurdex® (Allergan, Inc., USA)], with my primary indication of using the Dexamethasone implant in DME being, nonresponders to anti-VEGF without any associated vitreo macular traction (VMT). My second indication is in chronic DME. Other indications for anti-VEGF in DME as primary therapy are; in patients who have a history of recent coronary angioplasty or cerebrovascular accident or MI (<3 months). I also recommend intravitreal Fluocinolone implant (Iluvien ®, Alimera Sciences) in patients who respond to Dexamethasone implant but require repeated multiple injections.
| Concluding Remarks (Dr. syed Asghar Hussain)|| |
Corticosteroids modulate numerous interrelated pathways, linked to cellular damage from hyperglycemia and hypoxia affecting the blood–retinal barrier, including angiogenic growth factors and inflammatory cytokines; exerting a therapeutic effect in DME.,, In addition to this anti-inflammatory mechanism, corticosteroids alter the composition of endothelial basal membrane causing macular edema.,, The Fluocinolone Acetonide in Diabetic Macular Edema study and the Fluocinolone Acetonide in Human Aqueous studies have shown an improvement in the BCVA, from baseline values. Sustained release intravitreal corticosteroid injections (Ozurdex ® [Allergan, Inc., USA], Allergan) and (Iluvien ®, Alimera Sciences)], have a definite edge over IVTA since the drug efficacy is longer lasting in the former, as compared to the latter, which has a half-life of 18.6 days and may exert a clinical efficacy only for up to 3 months. The MEAD study showed a mean average reduction in central retinal thickness on OCT and improvement in the BCVA from baseline. The CHAMPLAIN study showed statistically and clinically significant improvements in BCVA and vascular leakage from DME at 26 weeks.
| What is the Management of Recalcitrant Diabetic Macular Edema?|| |
Dr. S. Natarajan: Systemic medical management should be stressed on. Factors such as high levels of blood glucose, hyperlipidemia, poor renal function, and hypertension can lead to recalcitrant DME. The assessment of posterior hyaloid status, whether there is traction on the macula or not, should be performed using OCT. In the case of DME with traction or taut posterior hyaloid with symptomatic VA disturbances, a vitrectomy can help with (a) Relieving the traction on macula, (b) Decrease in retinal thickening, and (c) Reduction in the levels of VEGF and similar cytokines present in vitreous. In case only one Anti-VEGF has been used, another stronger anti-VEGF or Ozurdex ® (Allergan, Inc., USA) can be tried. Some patients benefit from steroid rather than anti-VEGF. A repeat fundus fluorescein angiography (FFA) can be done after 3 months to note the status of macular perfusion. Macular ischemia has a poor prognosis.
Dr. N. Kasinathan: In cases of recalcitrant DME, one should perform FFA to look for macular ischemia, OCT, to check for the integrity of IS/OS junction and external limiting membrane, and to rule out surgical DME. One should monitor the systemic status for blood sugar control, nephropathy, systemic hypertension, and any other comorbid condition. One should either decide to switch over to another anti-VEGF, if there is no contraindication or else, switch over to intravitreal steroids. If the patient is a nonresponder after multiple injections or has a VMT or an epiretinal membrane (ERM), then one should proceed with vitrectomy.
Dr. Amjad Salman: The management of recalcitrant DME is challenging because both the patient and the ophthalmologist find it frustrating. It is important to give an adequate trial of therapy before giving up on that line of treatment. We would consider 3 doses of intravitreal anti-VEGF and adjunctive laser as the initial approach. If the DME has resolved but then recurred, more intravitreal anti-VEGF injections can be attempted. If the response to initial treatment has been poor and the CFT has failed to decrease by at least 30%, then intravitreal steroids can be tried. If this also proves to be ineffective, then pars plana vitrectomy (PPV) can be considered. It is important to note that sometimes cystoid spaces can reflect retinal degenerative changes in the absence of continued leakage. At each step, the patient should have a clear and realistic idea of the likely goals of treatment.
Dr. Nazimul Hussain: Whenever there is a case of recalcitrant DME, I would prefer to revisit the case and review all the FFA and OCT reports to understand the reasons for recalcitrant DME. Following which, I may do a review FFA, OCT, and OCT Angiography, to understand the reason for the recalcitrant response. It is quite obvious that, if OCT showed a thickened ERM or VMT or vitreomacular adhesion (VMA), then the approach is quite obvious for surgical management followed by pharmacological management if necessary. The assessment also includes patient's renal functions and control of diabetes which will impact the response, outcome and recurrence.
| Concluding Remarks (Dr. syed Asghar Hussain)|| |
DRCR.net Protocol I showed that more than 40% of Ranibizumab (Lucentis ®, Genentech)-treated eyes did not achieve complete resolution of DME. Control of systemic factors plays a critical role in the management of recalcitrant DME. Factors including elevated blood glucose, hyperlipidemia, hypertension, and poor renal status can contribute to persistent DME inspite of active treatment. Sustained release corticosteroid implants play a role in the treatment of recalcitrant DME unresponsive to anti-VEGF therapy. A combination of anti-VEGFs and corticosteroids, have been shown to be effective for recalcitrant DME. In addition, a taut posterior hyaloid has also been implicated in recalcitrant DME, for which intravitreal corticosteroids, enzymatic vitreolysis with Ocriplasmin (Jetrea ®, ThromboGenics Inc., USA) and vitrectomy, are the preferred treatments of choice.,,
| Role of Fundus Fluorescein Angiography Versus Optical Coherence Tomography Versus Optical Coherence Tomography Angiography-Changing Treatment Protocols|| |
Dr. S. Natarajan: FFA has a very prominent role in diagnosing abnormalities in the retinal circulation with respect to capillary nonperfusion, macular ischemia, leaking microaneurysms, and NVE. However, it has its own limitations with respect to quantifying macular edema, or identifying the deep retinal or choroidal circulation. It has several disadvantages due to its invasive nature and the use of fluorescein dye (viz., transient nausea, vomiting, allergic reactions, etc.). It is generally avoided in pregnancy and people who had a severe reaction to fluorescein dye in the past. It is also time-consuming.
OCT is a noncontact, noninvasive test, which provides a three-dimensional picture of the retinal layers including quantification of macular edema. It is extremely useful for the follow-up after intravitreal injections for DME. It supplements FFA very well for identifying CSME with leaking microaneurysms so that a targeted therapy can be advised.
Optical coherence tomography angiography (OCTA) is a newer noninvasive diagnostic imaging technique to evaluate the retinal circulation. It scans very fast as compared to the time taken in an FFA. It also provides more detailed information about superficial, deep retinal circulation as well as choriocapillaris. It also provides corresponding OCT images which complement the findings.
Advantages of OCTA versus FFA: OCTA is (a) noninvasive, hence can be used in people with allergies, known reactions to the dye as well as patients with compromised renal status, (b) It is a quicker procedure, (c) there is better imaging of preretinal NVZ, and (d) Deeper circulation is also captured.
Disadvantages of OCTA versus FFA: OCTA (a) Does not give information about leakage, pooling or peripheral capillary nonperfusion (b) Can miss microaneurysms due to slow blood flow (c) High cost of equipment.
Dr. N. Kasinathan: FFA is to be performed during the first visit, to assess the macular perfusion status and in the case of nonresponders. OCT is useful for follow-up visits and monthly/PRN injections. I have limited experience with OCTA.
Dr. Amjad Salman: FFA and OCT are both important investigations in the management of DME. OCT is more popular due to its noninvasive nature and ease of repeatability. FFA should be done in all cases of DME where it is not contraindicated as it provides valuable information regarding macular perfusion status. This indication may become less important with rising popularity of OCT angiography. OCT is essential in the management of DME. It gives an objective measurement of edema, response to therapy, the area of involvement, need for surgical intervention, etc., Managing DME in the absence of OCT is not advisable and often results in suboptimal outcomes. OCT can serve as guide to areas requiring laser also and obviate the need for repeated FFA.
Dr. Nazimul Hussain: There has been a wonderful changing paradigm shift in the investigative approach and treatment approach toward DR, based on the ocular investigations. At this point of time, I do Ultra widefield FA as a baseline, in all DR cases, diagnosed clinically as, moderate, severe, first-time CSME or suspicious PDR. Ultra-Widefield FA decides the need for Scatter laser PHC, whereas Macular FA at baseline lets us know about the character of leakage pattern as well as macular perfusion. Clinical management has improved a lot since the advent of OCT, which has helped us to decide the thickness change following anti-VEGF treatment and when to stop treatment. In other words, until the macula is dry. Topographic mapping of the macula using OCT has also helped to decide the area to be lasered, in patients with recurrent DME. OCTA in DME has helped us to assess the FAZ changes, both in superficial capillary plexus (SCP), and deep capillary plexus (DCP). OCTA in DME has shown that DCP undergoes the earliest changes in comparison to the SCP, which was not known before; hence suggesting the imminent risk of a decrease in vision inspite of the FA showing normal macular perfusion.
| Concluding Remarks (Dr. syed Asghar Hussain)|| |
Fluorescein angiography still remains the gold standard in the diagnosis of macular ischemia. OCT is a quick, noninvasive method of assessing retinal pathology. OCT angiography is a noninvasive technique to assess the retinochoroidal circulation using motion contrast imaging technique. Furthermore, split-spectrum amplitude decorrelation angiography along with OCTA allows us to view the retinal microvasculature, including DR pathology. Studies using OCTA have shown that it can demonstrate findings such as micro aneurysms, arteriolar wall staining, retinal NVZ, and Intra Retinal Microvascular Abnormalities., Hence, OCTA could prove to be the next paradigm shift in retinal investigative modalities for vascular disorders.
| When Should One Advise Pars Plana Vitrectomy in a Case of Diabetic Retinopathy?|| |
Dr. S. Natarajan: PPV is indicated in persistent vitreous hemorrhage. If both eyes have persistent vitreous hemorrhage, then vitrectomy is advised earlier than otherwise. PPV is also advocated in cases of traction retinal detachment involving macula, combined rhegmatogenous, and tractional detachment, one eyed patient with VH in seeing eye, ERM/Symptomatic VMA, Recalcitrant DME, anterior hyaloid proliferation, and Ghost cell glaucoma.
Dr. n. Kasinathan: ppv is Indicated in Nonclearing Vitreous Hemorrhage of 1 Month Duration, Trd Threatening the Macula, Complex Retinal Detachment, Vmt, Erm, and Intractable Dme.
Dr. Amjad Salman: PPV is done in 2 main settings in eyes with DME. First, when there is vitreomacular traction or a taut posterior hyaloid. Here, PPV is the only effective modality of treatment and should be performed in the patient's general condition permits. The results are good in both anatomic and functional outcomes. Second, when the macular edema has failed to respond to conventional treatment in the absence for significant VMT or taut posterior hyaloid. The rationale of PPV and ILM peeling here, is to allow the subretinal fluid to diffuse into the vitreous. In this indication, anatomical outcomes are better than functional results and visual acuity often fails to improve substantially.
Dr. Nazimul Hussain: There has been lot of advancement in instrumentation design and approach to management of surgical indications of DR. With these advancements and training of vitreoretinal surgeons in the world, the outcome of surgical management has improved tremendously then what was seen 2 decades ago. My indication for early vitrectomy in diabetics are as follows: (a) Recurrent VH (b) Vitreoretinal traction which incites recurrent VH (c) nonresolving VH (d) Early traction threatening macula (e) Thickened posterior vitreous face which impairs vision (f) Vitreomacular traction. The aforementioned are indications where vitrectomy is performed earlier. These have improved the outcome of surgery.
| Concluding Remarks (Dr. syed Asghar Hussain)|| |
The various indications for vitrectomy in DR are nonclearing VH, TRD involving the macula, recalcitrant DME, Premacular hemorrhage, combined Tractional and Rhegmatogenous Retinal Detachment, ERM, Anterior Segment NVZ, anterior hyaloid proliferation and ghost cell glaucoma, Taut posterior hyaloid membrane, VMT, and Taut ILM, to name a few.,,,,,
| Significance of Controlling Systemic Risk Factors in Diabetic Retinopathy|| |
Dr. S. Natarajan: Several studies have showed that there is an increased risk of DR, CSME and hard exudates in patients with high total cholesterol, high LDL cholesterol, and high triglycerides. Among them, the FIELD study demonstrated that patients with dyslipidemia receiving fenofibrate were less likely for progression of DR or developing DME. The ACCORD study concluded that rates of progression of DR were reduced with intensive glycemic control and control of hyperlipidemia; rather than control of hypertension. This further indicates that strict control of dyslipidemia and strict control of blood glucose (HbA1c <6.0%) work as adjunctive treatment for preventing the progression of DR or DME. Hence any patient with DR or DME needs to review systemic parameters with a physician and strict control of such derangements can additionally prevent progression of DR or development of DME.
Dr. N. Kasinathan: Controlling of systemic factors is important at all stages of disease but has to be specifically looked into when there is a delayed or no response to the treatment.
Dr. Amjad Salman: The importance of good glycemic control, control of hypertension, serum lipid levels, and renal dysfunction is impossible to overestimate. In many cases with mild to moderate DME, these measures alone are adequate to resolve the edema. Active management with the treating physician is always recommended.
Dr. Nazimul Hussain: Good glycemic control, control of systemic hypertension, dyslipidemia status, and renal status need to be closely monitored, on the lines of the Epidemiology of Diabetes Interventions and Control (EDIC), DCCT, and United Kingdom Prospective Diabetes Study (UKPDS).,,
| Concluding Remarks (Dr. syed Asghar Hussain)|| |
The DCCT (Diabetes Complications and Control Trial) and the UKPDS have shown that, in both type 1 and type 2 DM-affected individuals; the risk of developing DR is directly proportional to the systemic glycemic control, with a reduced risk of 76%. Furthermore, the EDIC trial showed a lesser rate of DME progression which required retinal photocoagulation; in the controlled glycemic status group versus those in the control group.,,
| General Conclusion|| |
In summation, the prevention and treatment of ocular complications of DR, involves the right combination of; control of systemic parameters, coupled with medical and surgical management, with the above-listed therapies. A sound knowledge of lasers, anti-VEGFs, corticosteroids and most importantly, the numerous clinical studies and trials is crucial, to achieving the optimum goal of vision preservation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gadkari SS, Maskati QB, Nayak BK. Prevalence of diabetic retinopathy in India: The all India ophthalmological society diabetic retinopathy eye screening study 2014. Indian J Ophthalmol 2016;64:38-44.
] [Full text]
Vitale S, Maguire MG, Murphy RP, Hiner CJ, Rourke L, Sackett C, et al.
Clinically significant macular edema in type I diabetes. Incidence and risk factors. Ophthalmology 1995;102:1170-6.
Techniques for scatter and local photocoagulation treatment of diabetic retinopathy: Early treatment diabetic retinopathy study report no 3. The Early Treatment Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin 1987;27:254-64.
Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, et al.
Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480-7.
Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 2003;22:1-29.
Williams JG, Trese MT, Williams GA, Hartzer MK. Autologous plasmin enzyme in the surgical management of diabetic retinopathy. Ophthalmology 2001;108:1902-5.
Azzolini C, D'Angelo A, Maestranzi G, Codenotti M, Della Valle P, Prati M, et al.
Intrasurgical plasmin enzyme in diabetic macular edema. Am J Ophthalmol 2004;138:560-6.
Diaz-Llopis M, Udaondo P, Arevalo F, Salom D, Garcia-Delpech S, Quijada A, et al.
Intravitreal plasmin without associated vitrectomy as a treatment for refractory diabetic macular edema. J Ocul Pharmacol Ther 2009;25:379-84.
Smith JM, Steel DH. Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No.: CD008214. doi: 10.1002/14651858.CD008214.pub2.
Tokida Y, Aratani Y, Morita A, Kitagawa Y. Production of two variant laminin forms by endothelial cells and shift of their relative levels by angiostatic steroids. J Biol Chem 1990;265:18123-9.
Ingber DE, Madri JA, Folkman J. A possible mechanism for inhibition of angiogenesis by angiostatic steroids: Induction of capillary basement membrane dissolution. Endocrinology 1986;119:1768-75.
Stokes CL, Weisz PB, Williams SK, Lauffenburger DA. Inhibition of microvascular endothelial cell migration by beta-cyclodextrin tetradecasulfate and hydrocortisone. Microvasc Res 1990;40:279-84.
Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd
, Friedman SM, et al.
Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2011;118:609-14.
de Carlo TE, Moult E, Choi W, Non-Neovascular Age- Related Macular Degeneration. In: Lumbroso B, ed., Clinical OCT Angiography Atlas, 1st
ed, New Delhi, India: Jaypee Brothers Medical Publishers, 2015;75-88.
Matsunaga DR, Yi JJ, De Koo LO, Ameri H, Puliafito CA, Kashani AH, et al.
Optical coherence tomography angiography of diabetic retinopathy in human subjects. Ophthalmic Surg Lasers Imaging Retina 2015;46:796-805.
Flynn HW Jr., Chew EY, Simons BD, Barton FB, Remaley NA, Ferris FL 3rd
, et al.
Pars plana vitrectomy in the early treatment diabetic retinopathy study. ETDRS report number 17. The Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1992;99:1351-7.
Shah SP, Patel M, Thomas D, Aldington S, Laidlaw DA. Factors predicting outcome of vitrectomy for diabetic macular oedema: Results of a prospective study. Br J Ophthalmol 2006;90:33-6.
Flaxel CJ, Edwards AR, Aiello LP, Arrigg PG, Beck RW, Bressler NM, et al.
Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: Diabetic retinopathy clinical research network. Retina 2010;30:1488-95.
Park JH, Woo SJ, Ha YJ, Yu HG. Effect of vitrectomy on macular microcirculation in patients with diffuse diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2009;247:1009-17.
Diabetic Retinopathy Clinical Research Network Writing Committee, Haller JA, Qin H, Apte RS, Beck RR, Bressler NM, et al.
Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology 2010;117:1087-93.e3.
Hoerauf H, Brüggemann A, Muecke M, Lüke J, Müller M, Stefánsson E, et al.
Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs. posterior hyaloid removal. A prospective randomized trial. Graefes Arch Clin Exp Ophthalmol 2011;249:997-1008.
Patel JI, Hykin PG, Schadt M, Luong V, Fitzke F, Gregor ZJ, et al.
Pars plana vitrectomy with and without peeling of the inner limiting membrane for diabetic macular edema. Retina 2006;26:5-13.
Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563-9.
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, Lachin JM, Genuth S, Cleary P, Davis MD, Nathan DM, et al.
Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000;342:381-9.
The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial. Arch Ophthalmol 1995;113:36-51.