3 Practical Aspects of Laser Therapy
DIABETIC MACULAR OEDEMA
If there is leakage of fluid at the centre of the retina this is termed macular oedema. Laser treatment is less effective but can still be worthwhile. The main aim of treatment is to prevent further visual loss. Laser treatment to the macula can occasionally itself cause visual loss so most people opt not to have laser unless they feel their vision has actually been affected even if the doctors can see a problem. Leakage of fluid causes blurring of vision in the centre. This problem progresses very slowly and therefore careful supervision is one way of managing people until they feel their vision is being affected. Treatment is usually guided by fluorescein angiography, a form of fundus photography where fluorescein is injected intravenously to delineate the integrity of the retinal blood vessels. This enables the doctor to work out where the leakage is and direct treatment to those areas. The effect of laser in this situation is slow and a response cannot often be seen for up to 4 months.
Diabetic Macular Oedema & The ETDRS
It is important to note four points when interpreting the results of the ETDRS:
- The ETDRS addressed primarily focal leakage and secondarily diffuse leakage
- All focal points of leakage between 500 microns and two disc diameters were treated directly
- Focal points located 300 to 500 microns from the centre could be treated if the vision was 20/40 or worse
- All treatment was guided by fluorescein angiography
- Clinically significant macular oedema was defined anatomically and also with respect to the amount of thickening
- REFERENCE THICKNESS = twice the diameter of a major retinal vein at the optic disc margin
- Treatment reduced the risk of visual loss of 3 lines or more on the ETDRS chart by 50%. The greatest benefit was in patients with visual acuity worse than 20/40. Visual gain was minimal.
ETDRS REPORT NO 4
ETDRS report No 4 notes that:
“If most of the leaks to be treated are close to the centre of the macula, the centre is uninvolved or only slightly thickened, and vision is normal or near normal, an initial period of observation may be preferable to immediate treatment. Deferral of treatment provides an opportunity for the patient to become more fully informed about the risks and potential benefits of treatment and for the base line visual acuity to be more completely documented. If the anatomical appearance of the macula worsens by even a small amount, the decision to proceed with treatment will be easier for both ophthalmologist and patient. If no worsening occurs, continuation of careful follow-up may provide an opportunity for the spontaneous improvement that occurs in some eyes, with avoidance of the risks of treatment close to the centre of the macula. These risks include inadvertent application of photocoagulation to the centre as well as spread of RPE degeneration to the center from nearby laser scars, which may occur in some eyes months or years after treatment”
“When retinal thickening, hard exudate, and leaks are all substantially farther than 500 microns from the centre of the macula, both the threat to the centre and the risk of treatment are small. If careful follow-up can be assured, deferral of treatment seems safe and may be preferred by some patients, but if there is any doubt about follow-up, prompt treatment may be the better choice”
PROLIFERATIVE DIABETIC RETINOPATHY
Laser treatment is very effective for dealing with new vessels. There are side effects and complications of laser but compared to total loss of sight in an affected eye these are a lesser of two evils. Most patients do not experience any side effects. Laser treatment is usually uncomfortable rather than painful. If the eye becomes very sore after treatment, especially if it turns red then the patient should return to the eye department without delay as occasionally angle closure glaucoma can be precipitated through dilation and occasionally iritis (inflammation of the iris) can occur through inadvertent burns to the iris. Giving codeine phosphate 60 mg orally 30-60 minutes before treatment helps many patients. If this is not enough then the eye can be anaesthetised with a local anaesthetic. This does not mean putting a needle into the eye. Very occasionally patients need a general anaesthetic. The disadvantage is that this requires hospital admission and a stay overnight. The laser used in theatre puts on larger burns so there are more likely to be side-effects and virtually all patients with new vessels require at least two treatments thus more than one general anaesthetic will be required.
Why Patients In The UK With Early Proliferative Diabetic Retinopathy Receive Laser
Patients in the UK with early proliferative diabetic retinopathy receive laser for the following reasons:
- For patients with type 2 diabetes, there is strong evidence that delaying treatment is associated with a worse visual prognosis
- Untreated early proliferative diabetic retinopathy has a very high rate of progression to high risk proliferative diabetic retinopathy
- Although the severity of non-proliferative or background retinopathy is a predictor for severe visual loss, in the absence of new vessel formation, it is difficult to determine the correct amount of laser treatment required.
- If new vessels elsewhere are not treated subsequent vitreous haemorrhage may make laser impossible subjecting the patient to all the risks and morbidity associated with vitrectomy
- If new vessels are not treated subsequent vitreous traction may threaten the macula necessitating a vitrectomy that could have been avoided by earlier laser treatment
- Modern lasers and treatment techniques, compared to those used in the DRS and ETDRS studies, are safer and have less deleterious effects on vision, particularly in the absence of significant macular ischaemia.
Most ophthalmologists in the UK believe that this changes the balance in favour of lasering patients with early proliferative retinopathy. This is reflected in the Royal College of Ophthalmologists 1997 guideline on diabetic retinopathy.
PATIENTS WITH TYPE 2 DIABETES MELLITUS DO BETTER WITH EARLIER TREATMENT
Recent additional analyses of visual outcome in ETDRS patients with severe NPDR to non-high-risk PDR suggest that the recommendation to consider scatter photocoagulation prior to the development of high-risk PDR is particularly appropriate for patients with type 2 diabetes.
The risk of severe vision loss or vitrectomy was reduced by 50% in those who were treated early compared with the deferral until high-risk PDR developed.
PROGRESSION FROM EARLY PROLIFERATIVE TO HIGH RISK PROLIFERATIVE RETINOPATHY IS ALMOST INEVITABLE
The ETDRS demonstrated a statistically significant reduction in severe visual loss (visual acuity less than 5/200) for those eyes with early treatment, especially for those patients with type 2 diabetes mellitus. However, in terms of severe visual impairment, the reduction was small and the risk was low in the deferral group.
| Classification | Cumulative rate (%) of High risk PDR | |||
| Baseline Retinopathy Severity Level |
No of eyes |
1-yr |
3-yrs |
5-yrs |
| mild NPDR (level < 35) |
609 |
0.8 |
6.7 |
15.5 |
| moderate NPDR (level 43) |
906 |
3.3 |
14.2 |
26.5 |
| moderate-severe NPDR (level 47) |
938 |
8.6 |
24.4 |
39.4 |
| severe NPDR (level 53A-D) |
500 |
14.6 |
39.5 |
56.0 |
| mild PDR (level 61) |
339 |
21.7 |
48.6 |
63.8 |
| very severe NPDR (level 53E) |
92 |
45.0 |
64.9 |
71.3 |
| moderate PDR (level >= 65) |
327 |
45.5 |
67.2 |
74.7 |
| Total |
3711 |
12.1 |
28.0 |
40.7 |
Note that severe NPDR and early PDR have similar high rates of progression. Very severe NPDR and moderate PDR (borderline high risk proliferative retinopathy) have even higher rates of progression.
Moderate PDR was defined as not having preliminary eligibility grading (neovascularisation at the optic disc (NVD) less than 1/4 to 1/3 disc area) but classified as having high-risk proliferative retinopathy on subsequent detailed grading.
It is clear from the above table, that the severity of non-proliferative or background retinopathy is a predictor for severe visual loss and this was confirmed by ETDRS report no 18. Although the severity of non-proliferative or background retinopathy is a predictor for severe visual loss, in the absence of new vessel formation, it is difficult to determine the correct amount of laser treatment required.
The ETDRS concluded that deferral of photocoagulation was preferable at least until retinopathy was approaching the high-risk stage (very severe NPDR or moderate PDR). However, eyes approaching this stage had almost a 50% risk of reaching it within 12 months:
- neovascularisation at the optic disc (NVD) less than 1/4 to 1/3 disc area
- and/or neovascularisation elsewhere (NVE) equal to or greater than 1/2 disc area, without vitreous or pre-retinal haemorrhage
PATIENTS TREATED WITH EARLY PROLIFERATIVE RETINOPATHY LOSE LESS VISION COMPARED TO PATIENTS TREATED WITH HIGH RISK PROLIFERATIVE RETINOPATHY
The DRS study showed that at 2 years, 11% of treated eyes and 26% of control eyes with high-risk retinopathy developed severe visual loss and that at 4 years 20% of treated eyes and 44% of control eyes developed severe visual loss (worse than 5/200). For early proliferative retinopathy- 3% of treated eyes and 7% of untreated eyes developed severe visual loss at 2 years and at 4 years 7% of treated eyes and 21% of untreated eyes developed severe visual loss. The DRS cautioned against treating patients with early-proliferative retinopathy and lesser levels of retinopathy because of the risk of laser itself. It should be remembered that many patients in this study were treated with xenon laser, a not particularly accurate device that produced very large burns. Modern laser treatment is more accurate and less “heavy” therefore clinicians are happier to treat patients at the early-proliferative stage.
MODERN LASER TREATMENT IS SAFER, PARTICULARLY IN THE ABSENCE OF SIGNIFICANT MACULAR ISCHAEMIA
According to the DRS 25% of patients receiving xenon laser had significant constriction of visual fields and 11% lost more than two lines of vision. Modern techniques are less “heavy” and patients are less likely to fail the legal requirements for driving11 Argon laser produces smaller, more accurate burns, and although side-effects do occur these are less common. This shifts the balance in favour of early laser treatment although there is evidence that visual field defects may be present even in the absence of laser. Laser treatment may still threaten visual acuity, particularly if the macula is ischaemic or oedematous. Patients with the more severe levels of non-proliferative retinopathy, even without new vessel formation, are at increased risks of severe visual impairment, however, such patients often have macular ischaemia. In such cases it may be prudent to closely observe and wait for the development of new vessels. At such a stage the case for laser treatment becomes more compelling, despite the potential reduction in central vision that may accompany pan-retinal photocoagulation.
4 Surgery
Surgery for diabetic retinopathy is only required if retinopathy has reached an advanced stage and is affecting vision. To some extent the need for surgery reflects failure to perform laser treatment appropriately and adequately at earlier stages of retinopathy. This may be the result of inadequate screening, poor assessment, inadequate treatment or poor patient compliance. Occasionally, despite laser treatment, patients progress to advanced diabetic retinopathy. This is particularly the case if new vessels are pulled forward by the vitreous. The main complications requiring surgery are persistent vitreous haemorrhage, retinal detachment and rubeotic glaucoma.
ADVANCED DIABETIC RETINOPATHY
Persistent vitreous haemorrhage, traction retinal detachment and rubeotic glaucoma are all advanced complications of diabetic retinopathy.
Persistent Vitreous Haemorrhage and Traction Retinal Detachment
Prior to vitrectomy persistent vitreous haemorrhage and traction retinal detachments threatening the fovea frequently led to severe visual impairment12
Vitrectomy not only clears the visual pathway and restores vision but it also removes the scaffold that new vessels grow upon.
Initially new vessels lie on the surface of the retina but later they become enmeshed in the posterior surface of the hyaloid surface of the vitreous. Localised detachment of the posterior vitreous results in traction on the new vessels forcing them to become elevated. Contraction of the detached posterior hyaloid surface results in traction on the retina leading in some cases to retinal detachment. Usually these traction retinal detachments are slowly progressive. More rapid progression can signify the presence of retinal holes and the development of rhegmatogenous retinal detachment.
DIABETIC RETINOPATHY VITRECTOMY STUDY (DRVS) 1998
Prior to the publication of this study patients with persistent vitreous haemorrhage were often not operated on until their haemorrhage had been present for at least one year. The DRVS found that eyes of patients with type 1 diabetes mellitus operated upon with in one to two months had significantly better visual outcomes compared to patients who had vitrectomy deferred for one year. The main benefit of early vitrectomy is entirely practical in that it allows macular oedema and proliferative retinopathy to be treated instead of continuing unchecked. For patients with type 2 diabetes mellitus the results were less convincing. This may be because these patients tend to also have less treatable forms of macular oedema at presentation. Furthermore proliferative retinopathy in type 2 diabetes mellitus tends to be less aggressive.
Traction retinal detachments are generally not operated on unless they involve the macula or they become rhegmatogenous. Vitrectomy is only of benefit if the macula has not been involved for more than six month13
Occasionally vitrectomy is performed for patients with widespread fibrovascular proliferation that progresses despite aggressive panretinal laser photocoagulation. Indications for early vitrectomy include >= three disc diameters fibrovascular tissue even in the absence of extensive panretinal laser photocoagulation. Fibrovascular proliferation on the anterior hyaloid surface may occur after vitrectomy in very ischaemic fundi, as the vitreous base cannot be removed fully without lensectomy. Further vitrectomy is usually required along with lensectomy and confluent laser photocoagulation to the peripheral retina and pars plana.
Rubeotic Glaucoma
Rubeotic glaucoma is a feared and often untreatable complication of proliferative diabetic retinopathy. In many cases the patient is left with a painful unseeing eye in which enucleation is often the final outcome.
Its forerunner, iris neovascularisation, usually, but not always, starts at the pupil margins before growing into the drainage angle.
Initially a membrane forms resulting in open angle glaucoma. This is rapidly followed by peripheral anterior synechia formation and intractable angle closure glaucoma. Prompt pan-retinal photocoagulation before the development of angle closure is the best chance of preventing its progression. Where the patient also has vitreous haemorrhage this may indicate the presence of retinal detachment and is an indication for urgent vitrectomy. Where this fails to prevent the development of glaucoma then augmented trabeculectomy with mitomycin-C or 5-Fluorouracil compares favourably with other surgical procedures such as Malteno tubes or cyclocryotherapy may be required if topical atropine and steroids fail to control the pain.
Rubeotic glaucoma can also be a complication of ocular ischaemia- one of the macroavascular complications of diabetes. In this situation there may be little capillary occlusion with new vessel formation stimulated by global ischaemia of the eye rather than just retinal ischaemia. In the setting of global ocular ischaemia pan-retinal photocoagulation is ineffective.