Clinical practice guideline - Ministry of Health
About the treatment of ocular diabetic complications
(Second revision)
Made by National Advisory Board of Ophthalmology
Authors: Németh J., Seres A., Récsán Zs
Summary
Ocular complications of diabetes mellitus occur in one-third of the patients and lead to severe
vision loss in case of every tenth diabetic patient. In our country, the second most frequent
cause of blindness is diabetic retinopathy which enhances the importance of this disease.
Based on the results of multicentric examinations, beyond the setting of optimal blood
pressure, serum glucose and lipid level, early ophthalmologic control and treatment in time
have a crucial role to avoid diabetic retinopathy and blindness. Ophthalmologic control of
patients is suggested annually or in every half year since diagnosis, then in preproliferative
retinopathy in every 2-4th month. In case of high-risk proliferative retinopathy we
recommend pan-retinal photocoagulation, in case of clinically significant macular edema,
laser photocoagulation or intravitreal VEGF injections are necessary.
I. Basic consideration
1. Introduction
Ocular complications of diabetes often lead to the most severe ocular outcome, to visual
deterioration, even to blindness.1-4 In Australia, based on the statistical data, the prevalence of
retinopathy is 21-36% and retinopathy combined with visual impairment is 6-13% among the
diabetic patients. According to the Wisconsin Epidemiologic Study of Diabetic Retinopathy,
almost every patient has some kind of retinopathy and 14-20% of patients aged 65-74 years
are blind after 30 years of diabetes mellitus. The annual incidence of retinopathy in Australien
diabetic people is 6-14%.5 This number is very similar to that in Hungary (16%). In
accordance with the statistical survey on blindness examined in 4 counties, about 1000 people
lose their vision of diabetic complications annually in Hungary, which is the second major
cause of blindness in this country.54-56 The number of blind people due to diabetes shows an
increasing tendency in Hungary representing the severity of the problem.54 Diabetes is a
systemic disease that the most frequently leads to blindness, which emphasizes the importance
of it. Most of the ocular sings are the consequences of microangiopathy.
Diabetes mellitus has several other ocular signs and complications which have influence on
diagnosis and in some cases quality of patients’ life. These complications are involved in
Table 1.
Guidelines of ocular screening, following, prevention and therapy of diabetic retinopathy
were elaborated, based on valid results of great multicentric studies (Table 2). In accordance
with the evidences, clinical practice guidelines were created in several countries.5-8 In this
present guideline, we introduce the facts and recommendations of international guidelines, the
last results of Hungarian studies and recommendations accepted by the consensus meeting of
Hungarian Diabetes Association on 19th June, 2004 and National Advisory Board of
Ophthalmology on 3rd June, 2005. The last actualisations recommended by the authors are
accepted by the National Advisory Board of Ophthalmology on 6th of January, 2012.
2. Stadiums and forms of diabetic retinopathy
In course of time, diabetic retinopathy develops in all patients in variable degree. Diabetic
retinopathy is divisible into the next stages:
1. Preretinopathy
Before the development of the well-known fundus alterations, preretinopathic changes occur
in the retina, which involves hemodynamic modification of the blood circulation and vessel
wall variations that break the integrity of blood-retina barrier.
2. Mild and moderate non-proliferative retinopathy or background retinopathy
The basic signs of stage 2 are retinal micro-aneurysms, intraretinal haemorrhages, lipoid
(hard) exudates, soft exudates (cotton-wool spots, micro-infarct of the retinal nerve fibre
layer) and edema.
3. Preproliferative retinopathy (severe non-proliferative retinopathy)
The number and extension of signs noticed in stage 2 on the fundus raises with aggravation of
ischemia and is defined as severe non-proliferative stage (4:2:1 rule):
More than 20 intraretinal haemorrhages in each of the 4 quadrants,
or
- venous beading in 2 or more quadrants
or
- prominent IRMA (intraretinal microvascular abnormality) in one or more quadrants.
4. Proliferative retinopathy
In this stage, neovascularisation starts from the optic nerve, just as elsewhere along or from
the retinal surface running to the vitreous which can lead to complications of vitreous
haemorrhage and threaten with traction retinal detachment.
The basic signs of proliferative retinopathy are:
Neovascularisation
– NVD (neovascularisation of the disc): neovascularisation on the optic disc or within 1disc
diameter of the optic nerve.
– NVE (neovascularisation of the retina elsewhere): neovascularisation in the retina, the
distance from the optic nerve is more than 1 disc diameter. Initially, the neovascularisation
is intraretinal, then braking through the internal limiting membrane it develops between
the posterior hyaloid membrane and the internal limiting membrane.
– NVI (neovascularisation of the iris): neovascularisation of the iris, anterior chamber angle
or both.
Sub-ILM haemorrhage: the haemorrhage detach the internal limiting membrane from other
part of the retina.
Subhyaloidal (retrohyaloidal) haemorrhage: real preretinal haemorrhage, haemorrhage
between the posterior hyaloid membrane and the internal limiting membrane.
Vitreous haemorrhage: haemorrhage in the vitreous gel.
Retinal detachment
– tractional retinal detachment
– combined tractional and rhegmatogen retinal detachment.
II. Diagnosis
1. Screening
Sorting of cases with retinopathy from diabetic patients is an important epidemiologic project.
Considering the underlying disease of these patients, cooperation is necessary between the
ophthalmologist and the specialist of the underlying disease such as physician, diabetologist,
endocrinologist, general practitioner. In the last decade, telemedicinal methods are available
for extensive ocular screening of diabetes.56
2. First examination and follow-up of the diabetic patients
Clinically and in order to avoid the ocular complications, ophthalmologic examination and the
required treatment at the proper time is essential. The main guidelines and the strength of
recommendations are involved in Table 3 and 4.
According to the Hungarian consent, the first ophthalmologic examination should be
performed immediately after the diagnosis of diabetes. At that time, a particular examination
through dilated pupil is required by an ophthalmologist.6 The first ophthalmic examination
contains the following elements:6
– best corrected visual acuity (A:I),
– intraocular pressure (A: III),
– gonioscopy (A: III),
– biomicroscopic examination of the anterior segment (A: III)
– stereoscopic examination of the posterior segment (fundus) through dilated pupil (A: I)
– examination of the peripheral retina and the vitreous (A: III)
3. Special supplemental examinations
Fundus photography
It is useful for documentation of the status, diagnosis of progression, evaluation of the
response to treatment. It is also a useful tool for telemedical screening.
Optical Coherence Tomography
A non-invasive method to examine the vitreo-retinal interface and the intra- and subretinal
space 47,48
Fluorescein angiography
It is not a routinely used procedure, since the macular edema, proliferative alterations are
well-diagnosable by biomicroscope in the main part of cases.
It is suggested:
– When planning to treat a clinically significant macular edema.
– In every cases, when visual deterioration is unexplainable by the statement of the fundus
(exploration of the ischemic maculopathy)
– In doubtful cases, to distinguish the neovascularisation from the IRMA (intraretinal
microvascular abnormalities)
Ultrasound examination
In case of increased opacity of optical elements, vitreous haemorrhage, it is definitely
suggested. Its use is worth considering, if we could not exclude retinal ablation by indirect
ophthalmoscopic, slit-lamp biomicroscopic examination.
Optical coherence tomography
This non-invasive method is well-applicable during examination of the vitreoretinal surface,
the retina and the subretinal space or in certain cases, to determine the indications of
vitreoretinal operations. It is an important research tool for adjudication of progression of
fundus diseases and efficiency of the applied treatment.47,48
III. Therapy
Proliferative retinopathy should be treated with laser photocoagulation, and in case of certain
complications, an operation may be necessary. Panretinal laser therapy decreases the release
of vasoproliferative material(s) and the oxygen need of peripheral retina due to its destruction,
causing the regression and scarring of neovascularization, decreasing the risk of vitreous
haemorrhage.13
Proliferative diabetic retinopathy is qualified as high risk according to the definition of DRS
(Diabetic Retinopathy Study Group), if the following exist:
– new vessels on the optic nerve head that are larger than one-third disc area
or
– new vessels in any size on the optic nerve head which are associated with vitreous or
preretinal haemorrhage
or
– new vessels elsewhere on the retina (not on the optic disc) that are larger than half disc
area, if they are associated with vitreous or preretinal haemorrhage.
In these circumstances the risk of visual loss is high and urgent panretinal laser treatment is
indispensable for the favourable outcome as proved by international randomized controlled
studies. 14-18
Panretinal photocoagulation reduces the risk for severe visual loss by 45% during a four-year
follow up in case of high risk proliferative retinopathy. The other therapy for proliferative
retinopathy is removing the vitreous humour (vitrectomy) performed if further complications
exist, such as removal of vitreous haemorrhage or fibrovascular tissue sticking on the retina
(membrane-peeling) or dissolving a retinal ablation. During vitrectomy, the panretinal laser
photocoagulation can also be performed in these eyes by endolaser.23-27 Vitrectomy is an
expensive, time-consuming, difficult operation with poor outcome in several eyes. However,
in case of vitreous haemorrhage with existing iris rubeosis or tractional retinal detachment
threatening or involving the macula, performing vitrectomy should be considered to stop or
slow the progression.
There are several researches on effectiveness of drugs that inhibit the neovascularization
(bevacizumab, ranimizumab) in connection with therapy of both proliferative retinopathy and
macular edema.
Macular edema
To any stadium except the first may relate diabetic maculopathy (macular edema or ischemic
maculopathy). Diabetic macular edema is more frequent in type II diabetes and this is the
main cause of visual loss in old patients. “Clinically significant” macular edema should be
enhanced, which is defined to include any of the following:
– thickening of the retina at or within 500 microns of the fovea,
or
– hard exudates at or within 500 microns of the fovea, if associated with thickening of the
retina,
or
– retinal thickening one disc area or larger, any part of which is within one disc diameter of
the fovea.
Since in case of clinically significant macular edema further visual loss has high risk, which
can be decreased by laser photocoagulation – as proved by a great national study (Early
Treatment Diabetic Retinopathy Study – ETDRS), laser treatment is required in all patients
even in those who have good visual acuity.19,21,41,42
This photocoagulation can be focal which treats the aneurysms, the leaking areas shown on
fluorescein angiography or grid with standard pattern affecting the pigmentepithelium of the
edematous area. The laser treatment of the macula reduces the risk of mild visual deterioration
due to clinically significant macular edema by 40% (experience of three-year-long followup).20,21
The other type of diabetic maculopathy is ischemic maculopathy, which means macular
capillary dropout associated with irreversible function loss that has no effective treatment. 21
New indications for vitrectomy are those cases of macular edema that are resistant for laser
photocoagulation and defined vitreomacular traction are demonstrable.
With intravitreal administration of triamcinolone acetonide, transient spectacular decrease is
accessible in the macular edema, however this method was not proved to be more effective
then the laser treatment.59
Diversified studies with extensive publications have been running for investigation and
verification of new therapies. 49-50
The recently approved intra-vitreal ranibizumab was proven more efficient than laser
treatment and also showed improved result as the natural course of the disease. On average
patients’ best corrected visual acuity improved by one line on average. 60 Its population-wide
application is limited by its high cost.
Ishaemic macular edema is the other form of diabetic maculopathy which shows the loss of
capillariy blood-flow in the macular area. It results in an irreversible visual loss. Currently
there is no effective treatment for this condition. 21 For cases of macular edema with vitreomaculat traction that doesn’t improve after laser treatment vitrectomy is recommended.
IV. Rehabilitation
Since in every case of severe bilateral visual deterioration or complete visual loss,
rehabilitation is particularly important which can give back the patients’ work capacity, the
possibility of self-sufficiency, enable to keep their usual lifestyle in changed living
conditions.58 This may mean the use of visual aid tools (optical rehabilitation: hand-held
magnifier, telescopic spectacle, reading machine, electronic aids, etc.) and in association with
these or individually, the functional vision assessment and vision rehabilitation according to
the patient’s needs, for example by learning compensatory techniques. Psychic aid is
important; furthermore, to meet the people with low vision their social, medical, legal,
educational and cultural opportunities.
V. Care process
Ophthalmological control is needed annually for patients with preretinopathy and in every
half year or annually in case of background (mild or moderate non-proliferative) retinopathy.
At this time, specific ophthalmological treatment is unreasonable, but the usual medical,
diabetological therapy and the optimal setting, including the exact control of blood sugar,
blood pressure and lipid status, are principally important.21, 43-46
In case of preproliferative (severe, non-proliferative) retinopathy and the non-high-risk
proliferative retinopathy, the chance for developing high-risk retinopathy is high, even it can
reach 75% and control is required in every 2-4 months. In these cases, if control of the patient
in every 2-4 months is not ensured, panretinal laser treatment is indicated.6
In case of high-risk proliferative retinopathy and clinically significant macular edema,
appropriate prompt laser treatment is suggested. 6
In case of pregnancy of diabetic patients, ophthalmological examination is necessary before
the conception (A: I), in the first trimester (A: I), then in every 1-12weeks (A: III), according
to the ophthalmological status. 6
In development and prognosis of diabetes, the previously mentioned general factors, such as
optimal blood sugar, blood pressure and lipid control, are of crucial importance. These facts
are confirmed by results of multicentric studies.2,21,22,30,31,36-40,43-46 Thus, the strict blood sugar
control reduces the amount of microvascular complications by 25%. Nevertheless, it is
important to know the observation that retinopathy may progress in the first two years after
introducing the strict blood sugar control.51
Reduction of HbA1C by 1% reduced the amount of required panretinal laser therapy by 37%.
On the other hand, the study revealed that the very strict control of blood pressure reduced the
necessity of photocoagulation by 35%; and reduction of blood pressure by 10mmHg reduced
the number of patients requiring photocoagulation by 11%.
Further risk factors that influence the progression of diabetic retinopathy are listed in Table 5.
To conclude, in case of diabetic retinopathy, the central vision can be preserved in 90% of
cases by performing appropriate laser treatment in time.53 According to our present
knowledge, in case of optimal blood sugar, blood pressure and lipid control, the severe vision
loss can be reduced from 60% under 20%, furthermore, more than half of the moderate vision
loss can be prevented by the currently available and timely applied ophthalmological
therapy.49 Nevertheless, we have to know the number of severe ophthalmic complications in
diabetes mellitus has not decreased in optimal degree.53
It has double reason:
1. blood sugar, blood pressure, lipid values differ from the optimal,
2. patients’ ophthalmologic control and therapy are not proceeded in time.
The panretinal laser treatment causes impairment in peripheral vision, visual field and may be
in night vision, which can contraindication for driving.18,53 The goals of laser therapy
confirmed by evidences are to slow the progression of retinopathy and vision loss. The
characteristic of this palliation is less expectable improvement, the microvascular
complications are only reduced by normoglycemia. Hence, the optimal diabetological setting
and the ophthalmological therapy in time are very important. However, the reality differs
from this ideal setting and optimal timing. It was introduced in London that the most patients
already had vision impairment at the first ophthalmological examination.46,53 Therefore, today
worldwide49 - and also in our country – the main challenge in prevention of diabetic
ophthalmic complications are to identify and send diabetic patients to prompt ophthalmologic
examination, control and if required, treat with laser, furthermore, to find and maintain the
optimal diabetological setting.
VI.Referencies
1. Klein, R, Klein, BE, Moss, SE: Visual impairment in diabetes. Ophthalmology 91: 1-9,
1984.
2. Klein, R, Klein, BE, Moss, SE, Cruickshanks, KJ: The Wisconsin Epidemiologic Study of
Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy
and associated risk factors in type 1 diabetes. Ophthalmology 105: 1801-1815, 1998.
3. Németh J, Süveges I: Vision 2020 – Világméretû program az elkerülhetõ vakság
felszámolására. Szerkesztõségi közlemény a Látás napja alkalmából. Szemészet 138: 115117, 2001.
4. Petõ T, Jánó I, B. Tóth B, Dégi R, Kolozsvári L: A diabetes mellitus szerepe a vakság
kialakulásában Csongrád megyében 1999-ben. Diabetol Hung 12: 51-55, 2004.
5. National Health and Medical Research Council: Management of Diabetic Retinopathy,
Clinical Practice Guidelines. 1997. June
6. Preferred Practice Pattern, Diabetic Retinopathy, American Academy of Ophthalmology
2008. Elérhetõ: http://one.aao.org/CE/PracticeGuidelines/PPP.aspx
7. A retinopathia diabetica ellátása. (In: Hatvani I /szerk./: Az Országos Szemészeti Intézet
módszertani útmutatója. OSZI, Budapest, 1999.) pp. 74-76.
8. Süveges I, Brooser G: A diabetes mellitus szemészeti szövõdményei. (In: Halmos T,
Jermendy Gy /szerk./: Diabetes mellitus. Elmélet és klinikum. Medicina Kiadó, Budapest,
2002.) pp. 424-449.
9. Bíró Zs, Kovács B: Diabeteszes maculaödéma „grid pattern” argon-laser kezelése.
Szemészet 128: 73-75, 1991. 10. Seres A, Papp A, Süveges I: A maculopathia diabetica
lézerkezelésérõl. Szemészet 137: 163-171, 2000.
11. Seres A: A diabétesz okozta vakság kezelésérõl és megelõzésérõl. Praxis 10: 56-58, 2001.
12. Vámosi P, Berta A: Diabeteszes betegeken végzett panretinalis lézer-photocoagulatio
hosszú távú követése, különös tekintettel a visus változására. Szemészet 136:257-261, 1999.
21. szám EGÉSZSÉGÜGYI KÖZLÖNY 3581
13. Diabetic Retinopathy Study: Report number 6: design, methods, and baseline results.
Report number 7: amodification of the Airlie House classification of diabetic retinopathy.
Invest Ophthalmol Vis Sci 21: 1-226, 1981.
14. The Diabetic Retinopathy Study Research Group: Preliminary report on effects of
photocoagulation therapy. Am J Ophthalmol 81: 383-396, 1976.
15. The Diabetic Retinopathy Study Research Group: Photocoagulation treatment of
proliferative diabetic retinopathy: the second report of Diabetic Retinopathy Study findings.
Ophthalmology 85: 82-106, 1978.
16. The Diabetic Retinopathy Study Research Group: Four risk factors for severe visual loss
in diabetic retinopathy. The third report from the Diabetic Retinopathy Study. Arch
Ophthalmol 97: 654-655, 1979.
17. The Diabetic Retinopathy Study Research Group: Photocoagulation treatment of
proliferative diabetic retinopathy: relationship of adverse treatment effects to retinopathy
severity. Diabetic Retinopathy Study report N°. 5. Dev Ophthalmol 2: 248-261, 1981.
18. The Diabetic Retinopathy Study Research Group: Photocoagulation treatment of
proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS)
findings, DRS report number 8.Ophthalmology 88: 583-600, 1981.
19. Early Treatment Diabetic Retinopathy Study Research Group: Photocoagulation for
diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 1. Arch
Ophthalmol 103: 1796, 1985.
20. Early Treatment Diabetic Retinopathy Study Research Group: Treatment techniques and
clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic
Retinopathy Study Report Number 2.Ophthalmology 94: 761-774, 1987.
21. Early Treatment Diabetic Retinopathy Study Research Group: Focal photocoagulation
treatment of diabetic macular edema. ETDRS Report Number 19. Arch Ophthalmol 113:
1144-1155, 1995.
22. Chew, EY, Klein, ML, Ferris, FL III, Remaley NA, Murphy RP, Chantry K, Hoogwerf
BJ, Miller D, Early Treatment Diabetic Retinopathy Study Research Group: Association of
elevated serum lipid levels with retinal hard exudate in diabetic
retinopathy. ETDRS Report 22. Arch Ophthalmol 114: 1079-1084, 1996.
23. Diabetic Retinopathy Vitrectomy Study Research Group:Two-year course of visual acuity
in severe proliferative diabetic retinopathy with conventional management.Diabetic
Retinopathy Vitrectomy Study (DRVS) re port 1.Ophthalmology 92: 492-502, 1985.
24. Diabetic Retinopathy Vitrectomy Study Research Group: Early vitrectomy for severe
vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic
Retinopathy Vitrectomy Study report 2.Ophthalmology 103: 1644-1652, 1985.
25. Diabetic Retinopathy Vitrectomy Study Research Group: Early vitrectomy for severe
proliferative diabetic retinopathy in eyes with useful vision. Results of a randomized trial.
Diabetic Retinopathy Vitrectomy Study report 3. Ophthalmology 95: 1307-1320, 1988.
26. Diabetic Retinopathy Vitrectomy Study Research Group: Early vitrectomy for severe
proliferative diabetic retinopathy in eyes with useful vision. Clinical application of results of a
randomized trial. Diabetic Retinopathy Vitrectomy Study report 4. Ophthalmology 95: 13211334,1988
27. Diabetic Retinopathy Vitrectomy Study Research Group:Early vitrectomy for severe
vitreous hemorrhage in diabetic retinopathy. Four-year results of a randomized trial: Diabetic
Retinopathy Vitrectomy Study report 5.Arch Ophthalmol 108: 958-964, 1990.
28. Diabetes Control and Complications Trial Research Group: The relationship of glycemic
exposure (HbA1c) to he risk of development and progression of retinopathy in the Diabetes
Control and Complications Trial. Diabetes 44: 968-983, 1995.
29. Diabetes Control and Complications Trial Research Group: Progression of retinopathy
with intensive versus conventional treatment in the Diabetes Control and Complications Trial.
Ophthalmology 102: 647-661, 1995.
30. Diabetes Control and Complications Trial Research Group: Lifetime benefits and costs of
intensive therapy as practiced in the Diabetes Control and Complications Trial. JAMA 276:
1409-1415, 1996.
31. Diabetes Control and Complications Trial Research Group: The effect of intensive
diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes
mellitus. Arch Ophthalmol 113: 36-51, 1995.
32. Diabetes Control and Complications Trial Research Group: The absence of a glycemic
threshold for the development of long-term complications: the perspective of the Diabetes
Control and Complications Trial. Diabetes 45: 1289-1298, 1996.3582 EGÉSZSÉGÜGYI
KÖZLÖNY 21. szám
33. The Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions
and Complications Research Group: Retinopathy and nephropathy in platients with type 1
diabetes four years after a trial of intensive therapy. N Engl J Med 342: 381-389, 2000.
34. Epidemiology of Diabetes Interventions and Comlications (EDIC). Design,
implementation, and preliminary results of a long-term follow-up of the Diabetes Control and
Complications Trial Cohort. Diabetes Care 22: 99-111, 1999.
35. The Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions
and Complications Research Group: Retinopathy and nephropathy in patients with type 1
diabetes four years after a trial of intensive therapy. Am J Ophthalmol 129: 704-705, 2000.
36. UK Prospective Diabetes Study Group: Tight blood pressure control and risk of
macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ
317:703-713, 1998.
37. UK Prospective Diabetes Study Group: Intensive blood glucose control with
sulphonylureas or insulin compared with conventional treatment and risk of complications
inpatients with type 2 diabetes (UKPDS 33). Lancet 352:837-853, 1998.
38. UK Prospective Diabetes Study Group: Efficacy of atenolol and captopril in reducing risk
of macrovasvular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 317:
713-720, 1998.
39. Kohner, EM, Stratton, IM, Aldington, SJ, Holman, RR, Matthews, DR: Relationship
between the severity of retinopathy and progression to photocoagulation in patients with type
2 diabetes mellitus in the UKPDS (U KPDS 52). Diabet Med 18: 178-184, 2001.
40. Kohner, EM, Aldington, SJ, Stratton, IM, Manley, SE, Holman, RR, Matthews, DR,
Turner, RC: United Kingdom Prospective Diabetes Study, 30: diabetic retinopathy at
diagnosis of non-insulin-dependent diabetes mellitus and associated risk factors. Arch
Ophthalmol 116: 297-303, 1998.
41. Roldán-Pallarés, M, El Bromboly, TK, Vilar-Maseda, NF: Visual function after
photocoagulation of diabetic macular edema with good visual acuity. Ann Ophthalmol 30:
361- 366, 1998.
42. Akduman, L, Olk, J: Laser photocoagulation of diabetic macular edema. Ophthalmic
Surgery and Lasers 28: 387- 408, 1997.
43. Klein, BE, Moss, SE, Klein, R, Surawicz, TS: The Wisconsin Epidemiologic Study of
Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard
exudate. Ophthalmology 98: 1261-1265, 1991.
44. Klein, R, Klein, BE, Moss, SE: Relation of glycemic control to diabetic microvascular
complications in diabetes mellitus. Ann Intern Med 124: 90-96, 1996.
45. Klein, R, Klein, BE, Moss, SE, Cruickshanks, KJ: Relationship of hyperglycemia to the
long term incidence and progression of diabetic retinopathy. Arch Intern Med 154: 21692178, 1994.
46. Klein, R: Prevention of visual loss from diabetic retinopathy. Surv Ophthalmol 47
(Suppl): S246-S252, 2002. 47. Hee MR, Puliafito CA, Duker JS: Topography of diabetic
macular edema with optical coherence tomography. Ophthalmology 105:360-370, 1998.
48. Nemes J, Somfai GM, Hargitai J: optikai koherencia tomográffal észlelt strukturális
változások diabeteses maculopathia miatt végzett fotokoaguláció után Szemészet,141:41-44,
2004.
49. Aiello, LM: Perspectives on Diabetic Retinopathy. Am J Ophthalmol 136: 122-135, 2003.
50. Fong, DS: Changing times for the management of diabetic retinopathy. Surv Ophthalmol
47 (Suppl): S238-S245, 2002. 51. KROC Collaborative Study Group: Diabetic retinopathy
after two years of intensified insulin treatment. JAMA 260:37, 1988.
52. Polak, BC, Dekker, JM, Moll, AC, Van Leiden, HA: Perspectives on diabetic retinopathy.
Am J Ophthalmol 136: 1193, 2003.
53. Kohner, E: Commentary: Treatment of diabetic retinopathy. BMJ 326: 1024-1025, 2003.
54. Németh J., Frigyik A., Vastag O., Göcze P., Petõ T., Elek I.: Vaksági okok
Magyarországon. Szemészet 142: 127-133, 2005.
55. Németh J., Seres A.: A cukorbetegség szemészeti szövõdményei. In: Winkler G.
(fõszerk.): Hatóanyagok, Készítmények, Terápia. Fókuszban a diabetológia. Melinda,
Budapest, 125-131, 2006.
56. Somfai G.M., Ferencz M., Fiedler O., Varga T., Somogyi A., Németh J.: Diabeteses
retinopathia a XXI. Század elején: prevenció, diagnosztika és terápia. Magyar Belorvosi
Archivum 62: 9-15, 2007.
57. Papp A., Pregun T., Szabó A., Schneider M., Seres A., Vargha P., Hagyó K., Németh J.:
Intravitreális triamcinolon-acetonid a diffuz diabeteses macula-oedema kezelésében.
Szemészet 144: 21-26, 2007. 21. szám EGÉSZSÉGÜGYI KÖZLÖNY 3583
58. Németh J.: Tanácsadó Szolgálat a Látássérültekért Magyarországon. Szerkesztõségi
közlemény. Szemészet 143: 137-138, 2006.
59. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing
intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular
edema. Ophthalmology, 2008 Sep;115(9):1445-6.
60.
http://www.ema.europa.eu/docs/hu_HU/document_library/EPAR__Summary_for_the_public/human/000715/WC500043548.pdf
61.
Massin P, Bandello F, Garweg JG, Hansen LL, Harding SP, Larsen M, Mitchell P,
Sharp D, Wolf-Schnurrbusch UE, Gekkieva M, Weichselberger A, Wolf S. Safety and
efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month,
randomized, controlled, double-masked, multicenter phase II study. Diabetes Care, 33: 2399405, 2010.
62.
Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO,
Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A. ; RESTORE study group. The
RESTORE study: ranibizumab monotherapy or combined with laser versus laser
monotherapy for diabetic macular edema. Ophthalmology, 118: 615-25, 2011.
Validity of the clinical medical guideline: 6th January, 2014.
VII. Appendix
Table 1. Ocular complications of diabetes mellitus
Extraocular
– Eyelid: blepharitis, xanthelasma
– External ocular muscles: paresis of abducens (IV) and/or oculomotorius(III) nerve
– Orbita: mucomycosis
– Conjunctiva: vasodilatation
Intraocular
– Cornea: decreased cornea sensitivity, slow-healing erosion, Descemet’s membrane
wrinkles
– Anterior chamber: melanin pigmentation
– Glaucoma: open angle glaucoma (more frequent incidence in diabetic people), secondary
glaucoma due to neovascularisation
– Rubeosis iridis (severe late complication with incidence of 0.25-10%)
– Corpus ciliare: impairment of accommodation
– Lens: temporary cataract, early development of senile cataract, diabetic snow flake
cataract
– Diabetic retinopathy
– Optic nerve: anterior ischemic optic neuropathy, acute papilla edema
Table 2. Multicentric studies examining the progression, prevention and treatment of diabetic
retinopathy
1980–1995 Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR)1,2
1971–1975 Diabetic Retinopathy Study (DRS)13-18
1979–1990 Early Treatment Diabetic Retinopathy Study (ETDRS)19-22
1979–1990 Diabetic Retinopathy Vitrectomy Study (DRVS)23-27
1983–1993 Diabetes Control and Complications Study (DCCT)28-35
1977–1999 United Kingdom Prospective Diabetes Study (UKPDS)36-40
2006-2011 Resolve61 és Restore62 clinical trials
Table 3. Advised timing of ophthalmologic control in diabetic people
1. Preretinopathy: annually (annual incidence of retinopathy: 5-10% ) (A: II)
2. Non-proliferative retinopathy: every 6-12 month (annual incidence of proliferative
retinopathy: 16%) (A: III)
Exception: clinically significant macular edema: immediate therapy (A: I)
3. Preproliferative retinopathy: control in every 2-4 month (A: I) or laser therapy (A: I)
(annual incidence of proliferative retinopathy: 75%)
4. Proliferative retinopathy: immediate therapy (A: I)
Table 4. Advised timing of ophthalmologic treatment in diabetic patients
1. Preretinopathy :optimal setting (blood sugar, blood pressure, lipids) (A: I)
Laser therapy is not reasonable in this stadium (A: III)
2. Non-proliferative retinopathy: optimal setting (blood sugar, blood pressure, lipids) (A: I)
Laser therapy is not reasonable in this stadium (A: III)
Exception: clinically significant macular edema: immediate laser therapy (A: I)
3. Preproliferative retinopathy: panretinal laser therapy (A: I), optimal setting (blood sugar,
blood pressure, lipids) (A: I)
4. Proliferative retinopathy: panretinal laser therapy (A: I), vitrectomy (A: III), optimal
setting (blood sugar, blood pressure, lipids) (A: I)
Table 5. Risk factors for progression of diabetic retinopathy49
1. Glycaemic control (insufficient)
2. Renal disease
3. Hypertension
4. Dyslipidaemia
5. Anaemia
6. Pregnancy
7. Nutrition abnormality
8. Obesity52