ORIGINAL ARTICLE

Change in Visual Acuity in Relation to Central

Macular Thickness after Intravitreal Bevacizumab in

Diabetic Macular Edema

Muhammad Ali Haider¹, Uzma Sattar²

^1-2Department of Ophthalmology, Rahbar Medical and Dental College, Lahore

ABSTRACT

Purpose: To evaluate the change in visual acuity (Log MAR) in relation to decrease in central macular thickness,

after a single dose of intravitreal Bevacizumab injection.

Study Design: Quasi experimental study.

Place and Duration of Study: Rahbar Medical & Dental College, Punjab Rangers Teaching Hospital, Lahore,

from January 2019 to June 2019.

Material and Methods: 70 eyes of 70 patients diagnosed with diabetic macular edema were included in the

study. Patients having high refractive errors (spherical equivalent of > ± 7.5D) and visual acuity worse than +1.2

or better than +0.2 on log MAR were excluded. Patients with ocular diseases other than diabetic macular edema

were also excluded. Central macular edema was measured in µm on OCT and visual acuity was documented

using Log MAR chart. These values were documented before and at 01 month after injection with intravitreal

Bevacizumab (1.25 mg in 0.05 ml). Wilcoxon Signed rank test was used to evaluate the difference in VA before

and after the anti-VEGF injection. Difference in visual acuity and macular edema (central) was observed,

analyzed and represented in p value. P value was considered statistically significant if it was less than 0.01%.

Results: Mean age of patients was 52.61 ± 1.3. Vision improved from 0.90 ± 0.02 to 0.84 ± 0.02 on log MAR

chart. The change was statistically significant with p value < 0.001. Central macular thickness reduced from 328 ±

14 to 283 ± 10.6 µm on OCT after intravitreal anti-VEGF, with significant p value < 0.001.

Conclusion: A 45 µm reduction in central macular thickness was associated with 0.1 Log MAR unit improvement

in visual acuity after intravitreal Bevacizumab in diabetic macular edema.

Key Words: Visual acuity, Macular edema, Central macular thickness, Bevacizumab.

How to Cite this Article: Haider MA, Sattar U. Zaidi SR. Change in Visual Acuity in Relation to Central Macular

Thickness after Intravitreal Bevacizumab in Diabetic Macular Edema. Pak J Ophthalmol. 2020, 36 (3): 292-297.

Doi: 10.36351/pjo.v36i3.1051

threatening condition. This increased thickness leads

to reduction in visual acuity. Currently, intravitreal

INTRODUCTION

Diabetic macular edema results in increased central

anti-VEGF drugs are recommended for management

retinal thickness at macula which is a sight

of diabetic macular edema¹. These drugs are safe,

decrease macular edema and restore vision. Amongst

Correspondence to: Muhammad Ali Haider

Department of Ophthalmology

Rahbar Medical and Dental College, Lahore

Email: alihaider_189@yahoo.com

the various anti-VEGF agents available, Bevacizumab

(1.25 mg in 0.05 ml) has revolutionized the

management of diabetic macular edema in recent

years. It is used off label in the developing world^2,3. It

is a humanized monoclonal antibody that swathes with

all isoforms of vascular endothelial growth factors-A,

Received: April 20, 2020

Accepted: June 17, 2020

Revised: May 8, 2020

292

Pakistan Journal of Ophthalmology, 2020, Vol. 36 (3): 292-297

Change in Visual Acuity in Relation to Central Macular Thickness after Intravitreal Bevacizumab in Diabetic Macular Edema

with a molecular mass of 149 kDa that effectively

status, slit lamp examination for anterior and

posterior segments was performed. Based on the

clinical findings diabetic macular edema was

diagnosed and the central macular thicknesswas

measured in micron meter (µm) on OCT (NIDEK

RS-3000 Advance). In selected patients, single

dose of intravitreal anti-VEGF was injected by

senior consultant ophthalmologist. Distance visual

acuity and OCT parameters were re-evaluated one

month after the intravitreal anti-VEGF therapy.

binds and inhibits all the isoforms of VEGF^4,5.

Significant decrease in leakage from vessels has also

been observed in proliferative diabetic retinopathy

treated with single dose of intravitreal Bevacizumab

(1.25 mg)⁶. It results in improved visual acuity (VA)

with reduction in macular thickness⁷. Anti-VEGF or

implantable dexamethasone with or without retinal

laser are considered to be the treatment of choice in

DME⁸.

Improvement in diabetic macular edema is gauged

by repeatedly measuring central retinal thickness,

before and after the start of treatment using high

resolution OCT (optical coherence tomography), a

Data was analyzed using SPSS version 22.

Quantitative data was represented as mean ± S.D.

and S.E. while the qualitative data was

represented in the form of pie chart.

diagnostic tool for management of retinal diseases^9,10

The aim of this prospective study was to correlate

the improvement in visual acuity with the

corresponding reduction in central macular thickness

after a single dose of intravitreal Bevacizumab therapy

in patients with diabetic macular edema.

RESULTS

A total of 70 eyes of 70 patients, 40 (57%) males and

30 (43%) females were enrolled in this research by

convenient sampling technique. Mean age of the

patients was 52.61 ± 1.3 with minimum age of 22

years and maximum 74 years (Table 1). Normality

MATERIAL AND METHODS

The study was conducted at the Department of

Table 1: Assumption Test of Normality Using Shapiro-Wilk.

Ophthalmology Rahbar Medical

Dental

Kolmogorov-Smirnov^aShapiro-Wilk

Statistic df Sig. Statistic Df Sig.

College, Punjab Rangers Teaching Hospital,

Lahore after approval from the ethical committee.

In this Quasi experimental study, 70 eyes with

diabetic macular edema were enrolled, having a

clear media for OCT with minimum of 3 mm

pupil diameter and best corrected visual acuity

(BCVA) of +0.2 to +1.2 on log MAR with snellen

equivalent of 6/12 to 6/120.

VA after injection

VA before injection

OCT before injection

OCT after injection

.160

.169

.255

.206

70 .000 .919

70 .000 .935

70 .000 .791

70 .000 .832

70 .000

70 .001

70 .000

assumption was checked by using Shapiro-Wilk test.

All quantitative variables were considered to have

normal distribution with p-value > 0.05 while the p-

value of ≤ 0.05 was considered as not normally

distributed. Shapiro-Wilk test shows abnormal

distribution of Visual acuity and macular

measurements (µm) on OCT (Table 2). There were

The patients having high refractive errors

(spherical equivalent of > ± 7.5D) and visual

acuity worse than +1.2 or better than +0.2 on log

MAR were excluded. Any other ocular condition

in which after treatment, the improvement in

vision was not significant (e.g. ocular

degenerative/dystrophic changes) and patients

having any media opacity that could affect the

visual acuity and OCT measurements were also

excluded.

Table 2: Descriptive Statistic of Age (Years).

In the selected patients, prior to intravitreal

injection of anti-VEGF, LogMAR distance visual

acuity was recorded and a full ophthalmological

examination including evaluation of refractive

Age of

patients

52.61 1.373 11.488

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Muhammad Ali Haider, et al

Table 3: Distribution of Macular Edema among Patients

different stages of diabetic retinopathy in 70 eyes.

Details are shown in table 3.

Having Different Types of Diabetic Retinopathy.

Type of Diabetic

Retinopathy

High risk PDR

Low risk PDR

Severe NPDR

Very severe NPDR

Total

Type of Macular Edema

Wilcoxon Signed rank test was used to evaluate

the difference in VA before and after the anti-VEGF

injection. It improved from 0.90 ± 0.02 to 0.84 ± 0.02

on log MAR chart. The change was statistically

significant with p value < 0.001. Central macular

thickness reduced from 328 ± 14 to 283 ± 10.6 µm on

OCT after intravitreal anti-VEGF, with significant p

value < 0.001 (Table 4).

CSMO

Diffuse

Total

Table 4: Description and Comparison in Visual Acuity and OCT.

Minimum Value Maximum Value

Mean Value

Statistics

Std.

Deviation

Range um

P value

Statistic

Statistics

VA before injection

VA after injection

OCT before injection

OCT after injection

1.0

0.9

490

319

215

161

1.3

1.2

705

480

.890

.840

328.43

283.44

.0261

.0278

14.348

10.672

.2181

.2324

120.041

89.287

< 0.001

Graph 1: Visual acuity before and after the intravitreal anti-VEGF

(Bevacizumab).

Graph 2: Macular thickness before and after intravitreal anti-VEGF

(Bevacizumab).

VA_A: Visual Acuity Before

VA_B: Visual Acuity After

OCT_A = OCT After Injection

OCT_B= OCT Before Injection

documented the correlational change after a single

injection of intravitreal bevacizumab injection between

visual acuity and central macular thickness on OCT.

DISCUSSION

Clinical evidence has established that increase in

central macular thickness in diabetic macular edema

results in corresponding decrease in visual acuity, and

the treatment which reduces the retinal thickening

improves vision. OCT can detect macular edema that

is not clinically evident, and several OCT-derived

biomarkers are useful predictors of its progression,

severity, and visual outcome¹¹. In this study, we

At any given central macular thickness, there was

a corresponding significant change in visual acuity.

Many eyes with significant macular edema had very

good visual acuity and eyes with mild edema exhibited

a profound decrease in vision. It is also reported that

there is inconsistence increase in thickness of central

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Change in Visual Acuity in Relation to Central Macular Thickness after Intravitreal Bevacizumab in Diabetic Macular Edema

macular point with the increase in visual acuity as well

was a significant improvement from baseline to

0.34+/-0.13, 0.25+/-0.12 and 0.17+/-0.12 Log MAR

units at 1 monthly intervals after the three injections.

At final visit at 6 months, the visual acuity was 0.16+/-

0.14 Log Mar units. With a P value of P > 0.0001, the

difference was statistically significant. The mean

central retinal thickness of central 1 mm area

improved from 452.9 +/- 143.1 microns at base linento

279.8 +/- 65.2 microns (P < 0.0001) on the final

visit.¹⁴Another study also suggested that Bevacizumab

is helpful in significant macular edema reduction and

visual acuity improvement in wet age related Macular

Degeneration.¹⁵

as incongruous decrease in thickness of central retina

with the decrease in visual acuity is not common.²

According to this, OCT measurement can be a good

surrogate for visual acuity in macular edema related to

diabetes.

Diabetic macular edema is the major clinical

factor affecting visual acuity in diabetic retinopathy

and is quantified for assessment and response to

treatment by the central retinal thickness measured by

OCT. Visual acuity is inversely related to the retinal

thickness to some extent. In this study we found a

strong correlation of visual acuity with OCT

measurements of macular thickness (r²= -0.46). After

the intravitreal bevacizumab therapy, the visual acuity

improved with the reduction in retinal thickness. This

study has shown that after a single dose of

Bevacizumab therapy the central retinal thickness on

OCT improved from 328 ± 14 to 283 ± 10.6 µm with a

corresponding improvement in the mean visual acuity

from 0.9 ± 0.02 to 0.84 ± 0.02 with significant p value

˂0.01.

In their study Santos et al. described the factors

affecting response to intravitreal anti-VEGF injections

in patients of diabetic macular edema. They found that

BCVA improved from 4.78 and 5.52 letters, and a

central retinal thickness decreased from 80.25 and

106.12 microns after 3 and 6 months of treatment.

They concluded that optimal responders to anti-VEGF

therapy could be identified based on their response to

decrease in central retinal thickness and hence, could

be a predictor of BCVA improvement after the

treatment¹⁶.

Recent studies have suggested that anti-VEGF

drugs are safe, cost effective, and easily admissible in

clinical settings, well tolerated by the patients and

remarkably well suited for treating macular edema

secondary to diabetes. The efficacy of bevacizumab

(1.25 mg) has been demonstrated in a study conducted

on patients having diabetic macular edema. There was

significant decrease in area of leaking vessels in

proliferative diabetic retinopathy when treated with

single dose of intravitreal bevacizumab (1.25 mg).

There was a significant improvement in mean visual

acuity associated with it⁸. These studies reported that

often in bilateral DME, Bevacizumab effects reduction

in macular thickness in un–injected fellow eye and

improvement in visual acuity was seen in 40% eyes

injected with Bevacizumab¹².

Mansourian et al determined the efficacy of a

single anti-VEGF injection of bevacizumab as primary

treatment for diabetic macular edema. They compared

the response to treatment using bevacizumab alone, in

combination with intravitreal triamcinolone acetonide

and compared the response to macular laser

photocoagulation. The result showed no significant

difference between these two treatments in reducing

the central macular thickness with improvement in

visual acuity¹⁷.

Yang et al compared the visual acuity, central

retinal thickness and retinal sensitivity in different

types of macular edema. He found that there was

positive correlation between central foveal thickness

and log MAR BCVA in patients with focal, diffuse

and ischemic diabetic macular edema (r = 0.56, -0.62;

P < 0.01).¹⁸

According to previous studies, significant

improvement of visual acuity was appreciated in

diabetic macular edema with Bevacizumab when

combined with dexamethasone, as compared to

Bevacizumab monotherapy¹³. In this study, efficacy of

treating diabetic macular with Anti-VEGF injection

bevacizumab in diabetic patients was documented.

Visual Acuity on Log MAR chart and central retinal

thickness on OCT were the efficacy markers that were

documented.

Recent studies showed that visual outcome

improves significantly if anti-VEGF therapy is started

earlier in the course of disease. Patients presenting

earlier with a shorter history of symptoms had better

improvement in visual acuity and sustained decrease in

central retinal thickness, 6 months after treatment.

However patients with a prolonged disease history, the

central retinal thickness and visual acuity at 3 months

The mean BCVA on Log MAR chart at the start of

the treatment was 0.42+/-0.14 Log MAR units. There

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Muhammad Ali Haider, et al

and 6 months post treatment would not be significantly

different from baseline values at the start of

treatment¹⁹. Thus, based on these results early

treatment of macular edema is indicated for better and

sustained anatomical and visual results. Thus earlier

detection of reduced visual acuity is significantly

important for the treatment of recurring macular

edema. Another study highlighted the correlation

between central subfield thickness and baseline visual

acuity after treatment with Bevacizumab²⁰.

REFERENCES

1. Bahrami B, Hong T, Gilles MC, Chang A. Anti-

VEGF Therapy for Diabetic Eye Diseases. Asia Pac J

Ophthalmol (Phila). 2017 Nov-Dec; 6 (6): 535-545.

Doi: 10.22608/APO.2017350.

2. Lam DS, Lai TY, Lee VY, Chan CK, Liu DT,

Mohamed S, et al. Efficacy of 1.25 MG versus 2.5 MG

intravitreal bevacizumab for diabetic macular edema:

six-month results of a randomized controlled trial.

Retina. 2009; 29 (3): 292-9.

3. Keane PA, Liakopoulos S, Chang KT, Wang M,

Dustin L, Walsh AC, et al. Relationship between

optical coherence tomography retinal parameters and

visual acuity in neovascular age-related macular

degeneration. Ophthalmology, 2008; 115 (12): 2206-

14.

4. Yang J, Wang X, Fuh G, Yu L, Wakshull E,

Khosraviani M, et al. Comparison of binding

characteristics and in vitro activities of three inhibitors

of vascular endothelial growth factor A. Mol Pharm.

2014; 11 (10): 3421-30.

Consistent with other studies, younger age of

patients with diabetic macular edema was associated

with significantly improved visual acuity^sand reduced

central retinal thickness after every 6 weeks of

treatment. However, if the treatment is delayed by

more than

6 weeks, repetition of intravitreal

bevacizumab would not result in significant visual

improvement²².

Limitation of our study was the small sample size.

We did not study the association of vascular patterns

of macula on OCTA with decreased visual acuity,

which is also a contributory factor in decreased visual

acuity.

5. Demirel S, Argo C, Agarwal A, Parriott J, Sepah

YJ, Do DV, et al. Updates on the Clinical Trials in

Diabetic Macular Edema. Middle East Afr

Ophthalmol. 2016; 23 (1): 3-12.

6. Pescosolido N, Pranno F, Buomprisco G. Intravitreal

injections and diabetic macular edema: actual and new

therapeutic options. Curr Diabetes Rev. 2013; 9 (6):

491-8.

7. Vyas S, Thapa R, Bajimaya S, Pradhan E, Paudyal

G. Anatomical and visual outcome of intravitreal

bevacizumab (Avastin) in patients with diabetic

macular edema. Nepal J Ophthalmol. 2016; 8 (15): 54-

61.

8. Das T, Aurora A, Chhablani J, Giridhar A, Kumar

A, Raman R, et al. Evidence-based review of diabetic

macular edema management: Consensus statement on

Indian treatment guidelines. Indian J Ophthalmol. 2016;

64 (1): 14-25.

9. Sala-Puigdollers A, Figueras-Roca M, Hereu M,

Hernandez T, Morato M, Adan A, et al. Repeatability

and reproducibility of retinal and choroidal thickness

measurements in Diabetic Macular Edema using Swept-

source Optical Coherence Tomography. PloS one,

2018; 13 (7): e0200819.

CONCLUSION

Thus based on our study results, 45µm reduction in

central macular thickness is associated with 0.1

LogMAR unit improvement in visual acuity in patients

with Diabetic Macular edema after a single dose of

Intravitreal Bevacizumab (1.25 mg).

Ethical Approval

The study was approved by the Institutional review

board/Ethical review board.

Conflict of Interest

Authors declared no conflict of interest.

10. Browning DJ, Glassman AR, Aiello LP, Beck RW,

Brown DM, et al. Diabetic Retinopathy Clinical

Research Network. Relationship between optical

coherence tomography-measured central retinal

thickness and visual acuity in diabetic macular edema.

Ophthalmology, 2007; 114 (3): 525-36.

Author’s Designation and Contribution

Muhammad Ali Haider; Assistant Professor: Study

Design, Data collection, Manuscript writing, and

review.

11. Bhende M, Shetty S, Parthasarathy MK, Ramya S.

Uzma Sattar; Optometrist: Compiling Results, Data

Analysis, Article review.

Optical coherence tomography:

guide to

interpretation of common macular diseases. Indian J

Ophthalmol. 2018; 66 (1): 20-35.

296

Pakistan Journal of Ophthalmology, 2020, Vol. 36 (3): 292-297

Change in Visual Acuity in Relation to Central Macular Thickness after Intravitreal Bevacizumab in Diabetic Macular Edema

Soheilian M. Using skew-symmetric mixed models for

investigating the effect of different diabetic macular

edema treatments by analyzing central macular

thickness and visual acuity responses. J Res Med Sci.

2011; 16 (10): 1319-25.

12. Hanhart J, Tiosano L, Averbukh E, Banin E, Hemo

I, Chowers I, et al. Fellow eye effect of unilateral

intravitreal bevacizumab injection in eyes with diabetic

macular edema. Eye, 2014; 28 (6): 646-53.

13. Maturi RK, Bleau L, Saunders J, Mubasher M,

Stewart MW.

12-Month, Single-Masked,

18. Yang XL, Zou HD, Xu X. Correlation of retinal

sensitivity, visual acuity and central macular thickness

in different types of diabetic macular edema. Chinese J

Ophthalmol. 2013; 49 (12): 1081-8.

19. Jeong SH, Kim JH, Kim JW, Lee TG, Kim CG, Yoo

SJ, et al. Patient's self-recognition of reduced visual

acuity due to recurrence of macular edema and prompt

visitation to the hospital in retinal vein occlusion.

Korean J Ophthalmol. 2014; 28 (3): 213-9.

20. Deak GG, Schmidt-Erfurth UM, Jampol LM.

Correlation of Central Retinal Thickness and Visual

Acuity in Diabetic Macular Edema. JAMA

Ophthalmology, 2018.

21. Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA,

Oden NL, King J, et al. Baseline Factors Associated

with 6-Month Visual Acuity and Retinal Thickness

Outcomes in Patients with Macular Edema Secondary

to Central Retinal Vein Occlusion or Hemiretinal Vein

Occlusion: SCORE2 Study Report4. JAMA

ophthalmology, 2017; 135 (6): 639-49.

Randomized Controlled Study of Eyes with Persistent

Diabetic Macular Edema after Multiple Anti-VEGF

Injections to Assess the Efficacy of the

Dexamethasone-Delayed Delivery System as an

Adjunct to Bevacizumab Compared with Continued

Bevacizumab Monotherapy. Retina, 2015; 35 (8):

1604-14.

14. Tareen IU, Rahman A, Mahar PS, Memon MS.

Primary effects of intravitreal bevacizumab in patients

with diabetic macular edema. Pak J Med Sci. 2013; 29

(4): 1018-22.

15. Ristic D, Vukosavljevic M, Draganic B, Cerovic V,

Petrovic N, Janicijevic-Petrovic M. The effect of

intravitreal administration of bevacizumab on macular

edema and visual acuity in age-related macular

degeneration

with

subfoveolar

choroidal

neovascularisation. Vojnosanitetski pregled. 2013; 70

(7): 660-3.

16. Santos AR, Gomes SC, Figueira J, Nunes S, Lobo

CL, Cunha-Vaz JG. Degree of decrease in central

retinal thickness predicts visual acuity response to

intravitreal ranibizumab in diabetic macular edema.

Ophthalmologica. 2014; 231 (1): 16-22.

22. Epstein DL, Algvere PV, von Wendt G, Seregard S,

Kvanta A. Benefit from bevacizumab for macular

edema in central retinal vein occlusion: twelve-month

results of

prospective, randomized study.

Ophthalmology, 2012; 119 (12): 2587-91.

17. Mansourian M, Kazemnejad A, Kazemi I, Zayeri F,

^.…^….

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