Diabetic macular edema (DME) is a major complication of diabetes mellitus that affects central vision. The symptoms of DME range from slight visual blurring to complete blindness if left untreated [
The worldwide prevalence of DME was reported as 6.81% among patients with diabetes [
Limited data are available on characteristics of DME patients in Turkey, and most data are from clinical trials. Only one multicenter registry examined the frequency of diabetic retinopathy and risk factors in Turkey. This previous study reported that the overall prevalence of DME was 3.4% in patients with newly diagnosed diabetes (
Real-life studies have high generalizability because, in contrast to randomized controlled trials, they provide data on real-life situations rather than on a specific set of patients who were selected under strict and controlled conditions [
A total of 945 consecutive patients (mean age ± SD: 61.3 ± 9.9 years, 55.2% male) with newly diagnosed DME were included in this national, multicenter, cross-sectional, noninterventional, observational, and single-visit study conducted at 36 retina centers across Turkey between March 2013 and July 2014. Study centers were well-equipped reference centers and were selected so that the study patients had geographical and other characteristics that were representative of Turkey in general.
All patients were at least 18 years old, had newly diagnosed DME, and received no previous DME-specific treatment. Patients who participated in a previous clinical study and those who already received or were currently receiving treatment for DME were excluded.
Each subject provided written informed consent for participation after being provided with a detailed explanation of the study objectives. The protocol of this study was approved by the institutional ethics committee and was conducted in accordance with the ethical principles stated in the “Declaration of Helsinki” and local regulations.
All patients were evaluated on a single visit, and data on demographics and medical history were recorded. This included history of diabetes (type, treatment, presence of systemic complications such as diabetic foot, time from onset to DME diagnosis, and follow-up care), hypertension and receipt of antihypertensive treatment, vital signs, body mass index (kg/m2), blood biochemistry, ocular history (reason for visiting an ophthalmologist, concomitant ocular diseases, and previous eye operations), ophthalmic examination findings including Early Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA), Snellen test score, type of DME (focal, diffuse, center-involving, clinically significant, and others), central macular thickness [CMT at the time of diagnosis via time domain (TD) and spectral domain (SD) optical coherence tomography (OCT)], and planned pharmacological treatments (corticosteroids, antivascular endothelial growth factor [anti-VEGF] agents) and nonpharmacological treatments (laser photocoagulation, vitrectomy).
Sample size calculation was performed using NCSS PASS 11 ver. 11.0.7 (Utah, USA). The results indicated that at least 900 patients from 36 centers should be included to achieve a confidence level of more than 95% and a statistical power of 80%, based on the patient enrollment capacity of the study centers (40 patients/year in high-capacity centers, 13 patients/year in low-capacity centers).
Statistical analysis was performed using SPSS (IBM Corp. 2012, IBM SPSS Statistics for Windows, version 21.0., Armonk, NY). When the data had nonnormal distributions, the Mann-Whitney
We enrolled 945 consecutive patients [mean (SD) age: 61.3 (9.9) years, 55.2% male], 96.4% with type 2 diabetes and 3.6% with type 1 diabetes (Table
Baseline characteristics of patients from Turkey with newly diagnosed diabetic macular edema.
|
61.3 (9.9; 20–88) | |
|
||
Male | 522 (55.2) | |
Female | 423 (44.8) | |
|
28.9 (5.4) | |
|
132.3 (15.6) | |
|
83.5 (11.6) | |
|
||
Present | 521 (55.1) | |
Undertreatmenta | 404 (77.5) | |
On dialysis | 13 (5.7) | |
|
||
Type 1 | 34 (3.6) | |
Type 2 | 911 (96.4) | |
Undertreatmentb | 619 (65.5) | |
Diabetic foot disease | 44 (4.7) | |
|
||
Less than 5 years | 113 (12.0) | |
5–9 years | 200 (21.2) | |
10–14 years | 279 (29.5) | |
15–19 years | 193 (20.4) | |
20 years + | 160 (16.9) | |
|
||
None (not followed up) | 165 (17.5) | |
Endocrinology | 267 (28.3) | |
Internal medicine | 444 (47.0) | |
Family practice | 65 (6.9) | |
Nephrology | 4 (0.4) | |
|
||
Fasting blood glucose (mg/dL) | ||
|
206 | |
Mean (SD) | 187.8 (81.9) | |
HbA1c (%) | ||
|
165 | |
Mean (SD) | 8.8 (2.3) | |
Total cholesterol (mg/dL) | ||
|
99 | |
Mean (SD) | 203.7 (61.2) | |
LDL (mg/dL) | ||
|
114 | |
Mean (SD) | 124.5 (42.0) | |
HDL (mg/dL) | ||
|
98 | |
Mean (SD) | 47.7 (21.3) | |
Triglyceride (mg/dL) | ||
|
113 | |
Median (min–max) | 142 (43–880) | |
Urea (mg/dL) | ||
|
127 | |
Median (min–max) | 28.8 (4.4–178) | |
Creatinine (mg/dL) | ||
|
140 | |
Median (min–max) | 0.9 (0.4–7.0) | |
Microalbuminuria (mg/dL) | ||
|
36 | |
Median (min–max) | 25 (0–741) |
Missing data for a27 and b130 patients.
Most patients visited an ophthalmologist due to vision problems (52.2%) rather than due to referral (Table
Ocular history of patients from Turkey with newly diagnosed diabetic macular edema.
|
|
Routine control | 360 (38.1) |
Vision problem | 493 (52.2) |
Consultation | 92 (9.7) |
|
|
No referral | 672 (71.1) |
Endocrinology | 108 (11.4) |
Internal medicine | 107 (11.3) |
Family medicine | 5 (0.5) |
Other | 53 (5.6) |
|
|
Cataract | 283 (29.9) |
Glaucoma | 36 (3.8) |
Other | 626 (66.2) |
|
162 (17.1) |
|
210 |
Cataract surgery | 194 (92.4) |
Vitrectomy | 4 (1.9) |
Fellow eye operations | 12 (5.7) |
During the study visit, fundoscopy was performed in 878 patients (92.9%) and fundus fluorescein angiography in 690 patients (73.0%) (Table
Ophthalmic examination findings of patients.
Right eye | Left eye | |||
---|---|---|---|---|
|
||||
|
36 | 35 | ||
Mean (SD) | 63.3 (58.5) | 68.4 (58.1) | ||
Median (min–max) | 56.5 (0–310) | 55 (0–280) | ||
|
||||
|
771 | 769 | ||
Mean (SD) | 0.5 (0.3) | 0.5 (0.3) | ||
Median (min–max) | 0.5 (0.05–1) | 0.5 (0.05–1) | ||
| ||||
1.0 logMAR (20/200) | 97 (12.6) | 92 (12) | ||
0.9 logMAR (20/158) | 43 (5.6) | 44 (5.7) | ||
0.8 logMAR (20/126) | 58 (7.5) | 69 (9) | ||
0.7 logMAR (20/100) | 69 (8.9) | 61 (7.9) | ||
0.6 logMAR (20/79) | 61 (7.9) | 58 (7.5) | ||
0.5 logMAR (20/63) | 76 (9.9) | 73 (9.5) | ||
0.4 logMAR (20/50) | 59 (7.7) | 71 (9.2) | ||
0.3 logMAR (20/39) | 67 (8.7) | 75 (9.8) | ||
0.2 logMAR (20/31) | 81 (10.5) | 78 (10.1) | ||
0.1 logMAR (20/25) | 75 (9.7) | 61 (7.9) | ||
<0.1 logMAR (20/22) | 85 (11) | 87 (11.3) | ||
|
15.5 (3.3) | 15.7 (3.8) | ||
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DME type, |
Right eye | Left eye | Both eyes | |
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||||
Diffuse | 403 (42.7) | 337 (35.7) | 740 (39.2) | |
Focal | 325 (34.4) | 371 (39.3) | 696 (36.9) | |
Mix | 93 (9.9) | 89 (9.4) | 182 (9.6) | |
Not defined | 120 (12.7) | 130 (13.8) | 250 (13.2) | |
Invisible fundus | 3 (0.3) | 17 (1.8) | 20 (1.1) | |
Totala | 944 (100.0) | 944 (100.0) | 1888 (100.0) | |
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Central macular thickness ( |
Right eye | Left eye | Both eyes | |
|
||||
At the time of diagnosis | ||||
|
912 | 901 | 1813 | |
Mean (SD) | 384.6 (144.0) | 377.7 (136.6) | 381.1 (140.4) | |
Time domain OCT | ||||
|
96 | 92 | — | |
Mean (SD) | 341.6 (129.0) | 342.0 (124.7) | — | |
Spectral domain OCT | ||||
|
812 | 805 | — | |
Mean (SD) | 389.3 (145.2) | 381.5 (137.6) | — | |
| ||||
≤300 |
298 (32.7) | 308 (34.2) | 606 (33.4) | |
>300 |
614 (67.3) | 593 (65.8) | 1207 (66.6) | |
Total | 912 (100.0) | 901 (100.0) | 1813 (100.0) |
aDue to the lack of data in 1 patient, analyses were for 1888 eyes in 944 patients.
bDue to the noninterventional design, data were available only for patients who had the test.
Intraocular pressure was measured in 655 patients (69.3%); this was determined by a pneumatic method in 459 patients (70.1%) and an applanation method in 196 patients (29.9%). The mean (SD) intraocular pressure was 15.5 (3.3) mmHg in the right eye and 15.7 (3.8) mmHg in the left eye (Table
The BCVA was measured using an ETDRS chart in 36 right eyes and in 35 left eyes and using a Snellen chart in 771 right eyes and in 769 left eyes. The mean (SD) ETDRS-BCVA was 63.3 (58.5) logMAR for the right eye and 68.4 (58.1) logMAR for the left eye in 36 patients. The mean (SD) Snellen score was 0.5 (0.3) for both eyes in 771 and in 769 patients (Table
Overall, 1888 eyes were examined. Diffuse DME was diagnosed in 39.2% of eyes and focal DME in 36.9% of eyes. At the time of diagnosis, the mean (SD) CMT was 381.1 ± 140.4
Laser photocoagulation therapy (32.1%) and anti-VEGF therapy (31.8%) were the most commonly preferred planned treatments, followed by anti-VEGF + laser photocoagulation therapy (30.8%) (Table
Planned treatments for the patients.
Treatment, |
Right eye | Left eye | Total |
---|---|---|---|
Anti-VEGF + laser | 264 (36.8) | 174 (24.6) | 438 (30.8) |
Anti-VEGF | 240 (33.5) | 213 (30.1) | 453 (31.8) |
Laser | 178 (24.8) | 279 (39.5) | 457 (32.1) |
Steroid + laser | 13 (1.8) | 10 (1.4) | 23 (1.6) |
Steroid | 4 (0.6) | 6 (0.8) | 9 (0.6) |
Vitrectomy | 3 (0.4) | 3 (0.4) | 7 (0.5) |
Steroid + anti-VEGF | 1 (0.1) | 1 (0.1) | 2 (0.1) |
Other | 14 (2.0) | 21 (3.0) | 35 (2.5) |
Total | 717 (100.0) | 707 (100.0) | 1424 (100.0) |
Patients who received antidiabetic treatment were significantly more likely to have type 1 diabetes (
Clinical characteristics of patients who did or did not receive antidiabetic treatment.
Antidiabetic treatment |
| ||
---|---|---|---|
No | Yes | ||
|
|||
Type 1 | 1 (3.1) | 31 (96.9) |
|
Type 2 | 195 (24.9) | 588 (74.1) | |
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|||
Less than 5 years | 27 (30.3) | 62 (69.7) |
|
5–9 years | 73 (40.8) | 106 (59.2) | |
10–14 years | 70 (29.2) | 170 (70.8) | |
15–19 years | 17 (9.9) | 154 (90.1) | |
20 years + | 9 (6.6) | 127 (93.4) | |
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|||
Smoking | 6 (9.1) | 60 (90.9) |
|
Used to smoke | 12 (6.2) | 183 (93.8) | |
Never smoked | 178 (32.1) | 376 (67.9) | |
|
|||
Not present | 151 (38.9) | 237 (61.1) |
|
Present | 45 (10.5) | 382 (89.5) | |
|
|||
Not present | 171 (32.3) | 358 (67.7) |
|
Present | 25 (8.7) | 261 (91.3) | |
|
|||
Diffuse | 121 (34.5) | 230 (65.5) |
|
Focal | 56 (19.3) | 234 (80.7) | |
Mixed | 10 (12.5) | 70 (87.5) | |
|
|||
Diffuse | 70 (24.8) | 212 (75.2) | 0.269 |
Focal | 99 (29.1) | 241 (70.9) | |
Mixed | 16 (21.3) | 59 (78.7) | |
|
|||
≤300 |
47 (17.4) | 222 (82.6) |
|
>300 |
147 (28.4) | 371 (71.6) | |
|
|||
≤300 |
42 (15.1) | 237 (84.9) |
|
>300 |
149 (29.9) | 349 (70.1) | |
|
376.5 (160–840) | 342 (146–999) |
|
|
370 (201–780) | 329 (148–999) |
|
CMT: central macular thickness; DME: diabetic macular edema.
Mann-Whitney
Patients who were not treated for diabetes were significantly more likely to have diffuse DME in the right eye (
The present TURK-DEM study is the first large-scale real-life observational clinical study of patients with newly diagnosed DME in Turkey. In line with the previous observation that DME has a higher prevalence in patients with type 2 diabetes than type 1 diabetes [
The time from diagnosis of diabetes to occurrence of DME was 10–19 years in half of recruited patients and less than 5 years in only 12.0% of the patients [
In line with the previously reported high prevalence of hypertension in patients with DME [
Ophthalmologists and physicians from other disciplines who care for patients with diabetes have an increased awareness of recent advances in DME management, and this may have helped to maximize the impact of these advances [
OCT was the most common method used for diagnosis of DME in our cohort (98.8%), followed by fundoscopy (92.9%). SD-OCT was used in most cases, and TD-OCT was only used in 10% of our patients. This seems notable given that pattern of edema classification on SD-OCT can have a significant impact on treatment decisions and subsequent visual outcome [
A previous case series indicated that diffuse DME was refractory to macular laser photocoagulation therapy [
Moreover, we found that 66.6% of the patients had baseline CMTs greater than 300
The two major nonsurgical treatments for diabetic retinopathy are retinal laser photocoagulation and pharmacologic approaches, including corticosteroids and VEGF inhibitors [
The major strength of this observational study is that we examined the records of 945 patients with DME from 36 centers throughout Turkey. This means that our findings are probably generalizable to the overall population of Turkey. The main limitation of our study is its observational design, because nonrandomized allocation might have led to bias and confounding. Nevertheless, given the paucity of reliable information on DME in Turkey, our findings provide important baseline data for a large representative sample of DME patients from Turkey and thus constitute a valuable contribution. More importantly, this study is the most comprehensive real-life investigation of newly diagnosed DME that employed detailed analysis of baseline characteristics and of the different tools and techniques used for diagnosis.
In conclusion, the present study is the first large-scale real-life registry of newly diagnosed DME patients in Turkey. Most of the patients in our cohort had type 2 diabetes, poor glycemic control, and concomitant systemic hypertension and were diagnosed with diabetes 10–19 years previously. A vision problem, rather than referral from another physician, was the most frequent reason for seeking care from an ophthalmologist. SD-OCT and fundoscopy were the most common diagnostic methods, and laser therapy and anti-VEGF therapy were the most common treatments. Two-thirds of patients had baseline CMT values greater than 300
Esat Ulay, M.D., and Gulsah Nomak, M.D., are Bayer Türk employees. Other authors declare that they have no conflict of interest.
This study was supported by Bayer Türk. The sponsor or funding organization participated in the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, preparation, review, and approval of the manuscript. The authors would like to thank Dr. Cagla Ayhan, M.D., and Professor Sule Oktay, M.D., Ph.D., from KAPPA Consultancy Training Research Ltd. (Istanbul, Turkey) who provided editorial support funded by Bayer Türk. TURK-DEM Study Group (by center name in descending order of number of patients enrolled) is comprised of the following: (1) Assoc. Prof. Banu Ozturk M.D.; Selcuk University Faculty of Medicine, Konya: (2) Assoc. Prof. Defne Kalayci, M.D., Mehmet Onen, M.D., Assoc. Prof. Mehmet Numan Alp, M.D.; Ankara Numune Traning and Research Hospital, Ankara: (3) Prof. Haluk Esgin, M.D.; Trakya University Faculty of Medicine, Edirne: (4) Prof. Ayse Oner, M.D., Neslihan Sinim, M.D.; Erciyes University Faculty of Medicine, Kayseri: (5) Prof. Ihsan Caca, M.D., Muhammed Sahin, M.D.; Dicle University Faculty of Medicine, Diyarbakir: (6) Assoc. Prof. Hurkan Kerimoglu, M.D., Prof. Kemal Gunduz, M.D., Gunhal Satirtav, M.D., Emine Tinkir M.D.; Necmettin Erbakan University Meram Faculty of Medicine, Konya: (7) Prof. Faruk Ozturk, M.D.; Ulucanlar Eye Training and Research Hospital, Ankara: (8) Assoc. Prof. Hidayet Erdol, M.D.; Karadeniz Teknik University Faculty of Medicine, Trabzon: (9) Prof. Umit Inan, M.D.; Afyon Kocatepe University Faculty of Medicine, Afyon: (10) Assoc. Prof. Feyza Onder, M.D., Dr. Melih Ustaoglu, M.D.; Haseki Traning and Research Hospital, Istanbul: (11) Prof. Cemil Apaydın, M.D., M. Erkan Dogan, M.D.; Akdeniz University Faculty of Medicine, Antalya: (12) Assoc. Prof. Nazife Sefi Yurdakul, M.D., Emine Deniz Egrilmez, M.D.; Izmir Ataturk Training and Research Hospital, Izmir: (13) Prof. Sengul Ozdek, M.D., Prof. Berati Hasanreisoglu, M.D., Prof. Gokhan Gurelik, M.D.; Gazi University Faculty of Medicine, Ankara: (14) Prof. Ali Osman Saatci, M.D., Prof. Ferit Hakan Oner, M.D.; Dokuz Eylul University Faculty of Medicine, Izmir: (15) Prof. Ibrahim Erbagci, M.D., Erol Coskun, M.D.; Gaziantep University Sahinbey Training and Research Hospital, Gaziantep: (16) Prof. Berkant Kaderli, M.D., Prof. Ahmet Ali Yucel, M.D., Assoc. Prof. Ozgur Yalcinbayir, M.D., Sertac Argun Kivanc, M.D.; Uludağ University Faculty of Medicine, Bursa: (17) Prof. Jale Mentes, M.D., Prof. Filiz Afrashi, M.D., Zafer Oztas, M.D.; Ege University Faculty of Medicine, Izmir: (18) Prof. Ozlem Sahin, M.D, Assoc. Prof. Semra Akkaya Turhan, M.D.; Marmara University Faculty of Medicine, Istanbul: (19) Bora Yuksel, M.D.; Izmir Bozyaka Training and Research Hospital, Izmir: (20) Prof. Bora Eldem, M.D., Prof. Sibel Kadayifcilar, M.D.; Hacettepe University Faculty of Medicine, Ankara: (21) Assoc. Prof. Nurullah Cagil, M.D., Dr. Yasin Toklu, M.D., Dr. Mucella Arikan Yorgun, M.D.; Yildirim Beyazit University Faculty of Medicine Ataturk Traning and Research Hospital, Ankara: (22) Assoc. Prof. Nurten Unlu, M.D., Dr. Guney Guner, M.D.; Ankara Traning and Research Hospital, Ankara: (23) Prof. Emin Ozmert, M.D., Prof. Figen Sermet, M.D., Assistant Prof. Sibel Demirel, M.D.; Ankara University Faculty of Medicine, Ankara: (24) Prof. Ayse Nihal Demircan, M.D., Selcuk Sizmaz, M.D., Ebru Esen, M.D.; Cukurova University Faculty of Medicine, Adana: (25) Assoc. Prof. Murat Sonmez, M.D; Gulhane Military Medical Academiy Haydarpasa Training and Research Hospital, Istanbul: (26) Prof. Gursel Yılmaz, M.D., Assoc. Prof. Imran Akkoyun, M.D., Ali Kucukoduk, M.D.; Ankara Baskent University Hospital, Ankara: (27) Prof. Sema Oruc Dundar, M.D., Harun Cakmak, M.D.; Adnan Menderes University Training and Research Hospital, Aydin: (28) Assoc. Prof. Levent Karabas, M.D., Ozgur Kara, M.D.; Kocaeli University Faculty of Medicine, Kocaeli: (29) Prof. Ibrahim Kocer, M.D.; Ataturk University Yakutiye Training and Research Hospital, Erzurum: (30) Prof. Yüksel Sullu, M.D., Tuba Cetinkaya, M.D.; Ondokuz Mayis University Faculty of Medicine, Samsun: (31) Prof. Nazmiye Erol, M.D., Mustafa Deger Bilgec, M.D.; Eskisehir Osmangazi University Faculty of Medicine, Eskisehir: (32) Prof. Ali Hakan Durukan, M.D., Dr. Soner Guven, M.D.; Ankara Gulhane Military Medical Academy, Ankara: (33) Assist. Prof. Rıfat Rasier, M.D., Dr. Onur Temizsoylu, M.D., Dr. Nazlı Gul Yalcin, M.D.; Bilim University Florence Nightingale Hospital, Istanbul: (34) Prof. Nur Kir, M.D., Zafer Cebeci, M.D.; Istanbul University Istanbul Faculty of Medicine, Istanbul: (35) Prof. Sema Arvas, M.D., Ahmet Sarici, M.D.; Istanbul University Cerrahpasa Faculty of Medicine, Istanbul: (36) Assoc. Prof. Ufuk Adiguzel, M.D.; Mersin University Faculty of Medicine, Mersin.