Epidemiological profile of age-related macular degeneration patients in Federal University of Parana , Brazil

Objective: To evaluate the profile and severity of age-related macular degeneration (AMD) in ophthalmology ambulatory of Federal University of Parana in Curitiba, Parana, Brazil. Methods: This was a cross-sectional study with data collected among the 6155 outpatients ophthalmic appointments (november 2011 to november 2013). In this 6155 patients, a total of 346 patients had retinal diseases and were screened by two retinal specialists for signs of AMD. If present, they were submitted to a protocol including a new ophthalmic evaluation comprising visual acuity, tonometry, biomicroscopy, dilated fundus examination and optical coherence tomography (OCT). Results: A total of 6155 patients underwent ophthalmologic evaluation for several reasons. Three hundred and forty six patients had retinal diseases (incidence of 5.6%) and 68 of these (incidence of 19.6% in retinal patients) had AMD. The mean age of all patients was 53 years and in retinal patients was 60 years. In AMD patients mean age was 73 years. Ethnicity, body-mass index (BMI) and smoking habits were evaluated in the 68 patients diagnosed with AMD (34 exudative and 34 non-exudative) but none of those parameters were statistically significant comparing exudative and non-exudative forms. Conclusion: Most of the patients were European descendants. A higher proportion of advanced cases of AMD comparing with literature was found (50% of exudative form). Regarding ethnicity, iris color, smoking habit and BMI, there was no difference comparing exudative and non-exudative forms. These results may be compared to available AMD studies, since there is little information about AMD in Brazil.


INTRODUCTION
A ge-related macular degeneration (AMD) is a multifactorial disease, with an increasing prevalence worldwide and significant morbidity.The first studies, in the early 1980s, pointed to the significant burden that AMD would represent in the years to come.The AMD is the leading cause of legal blindness in the Western world in people over 50 years old. (1)Only in United States (US), 9.2% of the population over 40 years have signs of AMD (2) .In France, AMD is the leading cause of blindness in population over 50 years, with a prevalence of 8.50% and increasing with age reaching up to 27.9% in people over 75 years (3,4) .It decreases the reading and driving abilities, as well as all activities that need an accurate sight (5,6) .It is expected a 50% increase in number of individuals affected by AMD until 2020 (7) .
There is no official epidemiologic statistic of AMD in Brazil but some studies suggest numbers (8) .In a recent global metaanalysis including 149 studies, only 39 used international protocols of screening and imaging and were considered reliable.In this meta-analysis, only one was from Latin America (9) .This study, held in Londrina, Brazil, indicate a prevalence of 15.1% of AMD in that population over 60 years.Another study held Veranópolis, Brazil, showed an AMD prevalence of 30.5% in patients above 80 years, but was not included in global data due to its methodology (9) .It is important to note that both Brazilian studies collected data from specific groups (eastern descent or older than 80 years) (10,11) .The Brazilian Institute of Geography and Statistics estimated approximately 285 thousand inhabitants over 55 years old in Curitiba, Paraná, Brazil in 2013 (12) .Applying an estimated AMD prevalence of 6 to 10% (Europe and US), it is expected around 17 to 28 thousand cases -all forms of AMD -in Curitiba, Brazil.
Age is the major risk factor for AMD.Studies indicate an oxidative damage of retinal pigmented epithelium (RPE) and choriocapillaris, including a decrease in plasmatic levels of glutathione, C and E vitamins and catalase activity.An increase in lipofuscin levels in RPE was observed too (13,14) .However a variety of factors are involved in its pathogenesis.The hereditary polygenic component is among the main risk factors for developing the disease (15,16) , and a variety of other factors are involved, including ethnicity, genetics (17,18) , family history, exposure to UVB rays, vitamins deficiency (19) , high body mass index (BMI; range 25 to 30 -overweight and > 30 -obese) and smoking. (20)n this study we tried to assess the epidemiological profile of AMD and the presence of known risk factors in AMD cases, such as age, obesity, ethnicity and smoking habits.

METHODS
This is a cross-sectional study conducted according to the Declaration of Helsinki.All patients were submitted to a written informed consent and examined by two retina specialists in vision center at the Federal University of Paraná.The study was approved by ethics committee of Clinical Hospital, Federal University of Parana, in Curitiba, Brazil.
Patients were recruited from november 2011 to november 2013, during the regularly scheduled ophthalmologic evaluation at the "Vision Center" -Department of Ophthalmology -Federal University of Paraná in Curitiba; Brazil.Patients with any retinal suspicious characteristics were evaluated by two retina specialists and were included in the study only if met the following criteria: • Age above 55 years; than -4.00 diopters with signs of retinal degenerations such as lacquer cracks, posterior staphyloma, tilted optic disc, retinoschisis etc).All patients underwent a complete ophthalmologic examination including a best corrected visual acuity test using an ETDRS "model 2" chart™ (Good-Lite, Elgin, IL) without mydriasis, biomicroscopy using a Topcon SL-1E™ slit lamp (Topcon, Oakland, NJ), Goldmann tonometry and a fundus exam after mydriasis with tropicamide, performed by a retina specialist using a Heine EN30™ indirect ophthalmoscope (Heine, Kientalstraße 7, Herrsching) and a Volk™ 20 diopters lens (Volk, Mentor, OH).Patients who met the study criteria were submitted to an optical coherence tomography (OCT) image from both eyes with specific image protocol using a Zeiss Stratus OCT™ (software version 4.0.2,Macular Normative Data Feature MAC-3244 -Carl Zeiss Meditec, Göschwitzer Straße, Jena).
Finally, the AMD patients were classified as non-exudative ("dry") if macular drusen with at least 62μm were found.If signs of choroidal neovascularization (active bleeding or history of previous intravitreal therapy, etc.) were found, they were included as exudative ("wet" form).

Imaging Protocol
In order to ensure that AMD patients had the specified criteria and no other macular disease, an OCT image was performed for each patient, using a protocol according to "University of Wisconsin -School of Medicine and Public Health -Fundus Photograph Reading Center -Non-study Specific Stratus Optical Coherence Tomography (OCT 3)".Two scan types were performed: the Fast Macular Thickness Map scan and the Cross Hair scan.All subjects had one Fast Macular Thickness Map (centered on macula, the retinal boundaries indicated by white lines on the underlying scans (the internal limiting membrane and the retinal pigment epithelium) did not contain obvious major errors at the center of the macula) and a 6mm Cross Hair scan centered on foveal region.A minimal signal strength of 5 was necessary.

Statistical analysis
Estimated cases of AMD in Curitiba (city in south region of Brazil) using demographic features of Brazilian census in 2014.In order to set de confidence interval found, an online calculator was used (21) .For data analysis, Prism 6.0c™ (GraphPad Software, La Jolla, CA, USA 2013) was used, t-test, Fisher exact test, Oneway ANOVA (Analysis of Variance) Tukey's post hoc or Quisquare test used to single and demographics comparisons (age, ethnicity, gender, smoking habit and BMI).Values under 5% were considered significant.
A total of 6155 patients underwent ophthalmologic examination from november 2011 to november 2013 in vision center at Federal University of Parana.Three hundred and forty six of them had suspected retinal diseases and were evaluated by two retina specialists.Any suspected case of AMD was submitted to the protocol already described.

RESULTS
In these 2 years, a total of 68 patients with AMD and no other conditions that could somehow interfere in diagnosis and stagingsuch as diabetes -were included.The mean age of outpatients group was 53 years (SD±22; range 0 -102 years).In the retina group was 60 years (SD±15; range 0-88 years) and AMD group was 73 years (SD±8.2;range 55-88 years).If these groups are compared, there was a significant difference in mean age among them.Comparing outpatients, retina patients and AMD with each other, a significant difference was found (p<0.001,ANOVA).Furthermore, there was a larger number of female patients in all groups.In outpatients, 3941 (64%) were female, while in retina was 181 (52%) and AMD was 35 (51%) Table 1 and Figures 1A and 1B.The AMD group included 68 subjects (63 European descendants and 5 Afro-descendants, 33 men and 35 women), being 34 with exudative form and 34 with non-exudative.There was no significant difference for age, gender or BMI among the groups.Regarding the age, comparing both groups, a mean of 73 years (SD±7.7;range 55-88 years) was found in non-exudative AMD and a mean of 73 years (SD±8.8;range 55-88 years) in exudative.A slightly predominance of females in non-exudative AMD (53%) and an equal number in exudative (50%).A larger number of European descendants in both non-exudative (91%) and exudative (94%) was observed, without difference in groups however.Regarding the iris color, a higher number of patients with a light iris (either blue or green) was found in the exudative group comparing to the non-exudative (p = 0.0506).A well known risk factor for AMD, smoking habit, was not different in AMD groups.Nevertheless, a higher percentage of smokers in exudative against non-exudative group (44% vs. 29%) was found.Finally, the overweight patients outscored the normal weight patients in both groups; 53% in non-exudative and 56% in exudative; but no difference comparing groups was observed, as shown on table 2. professionals about it, makes it a great challenge to know the real incidence.We believe that reliable data could guide public policies of early diagnosis and treatment, resulting a lower morbidity with better financial and social cost outcomes (29)(30)(31)(32)(33) .
Age-related macular degeneration is serious sight-threatening disease.Nevertheless, there is little information about the real impact of it in Brazil, even in major ophthalmology services.We hope that these data can help to facilitate the access of AMD early disease cases as well, preserving the patients sight and quality of life.

CONCLUSION
Most of the patients were European descendants.A higher proportion of advanced cases of AMD comparing with literature were found (50% of exudative form).Regarding ethnicity, smoking habit and BMI, there was no difference comparing exudative and non-exudative forms.These results may be compared to available AMD studies, since there is little information about AMD in Brazil.

Figures 1A :
Figures 1A: Age average and standard deviation; and 1B.Gender proportions in groups Epidemiological profile of age-related macular degeneration patients in Federal University of Parana, Brazil (>125 μm) in both eyes or one eye with large drusen and fellow eye with either geographic atrophy (> 360 μm) or signs of choroidal neovascularization; • No eye disease other than previous cataract uncompli- • History of AMD presenting large confluent soft drusen Rev Bras Oftalmol.2016; 75 (5): 352-5