International Journal of Retina (IJRETINA) 2025.
Volume 8.
Number 2.
P-ISSN.
E-ISSN.
REAL-WORLD EVALUATION OF THE EFFECTIVENESS OF
INTRAVITREAL BEVACIZUMAB INJECTION FOR
NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AT
CIPTO MANGUNKUSUMO NATIONAL REFERRAL HOSPITAL
Gitalisa Andayani Adriono1,2.
Indra Maharddhika Pambudy2.
Andi Arus Victor1.
Ari Djatikusumo1.
Anggun Rama Yudhanta1.
Mario Marbungaran Hutapea1,2.
Ichsan Fauzi Triyoga3 Department of Ophthalmology.
Faculty of Medicine.
Universitas Indonesia.
Kirana Eye Center - Cipto Mangunkusumo National General Hospital.
Jakarta.
Indonesia JEC Eye Hospitals & Clinics.
Jakarta.
Indonesia Faculty of Medicine.
University of Indonesia.
Jakarta.
Indonesia Abstract Introduction: Neovascular age-related macular degeneration .
AMD) is a leading cause of visual impairment globally.
While intravitreal anti-VEGF therapy is the standard treatment, real-world data on bevacizumab (IVB), the most accessible agent in Indonesian public hospitals despite being off-label, remains limited.
This study aims to evaluate the effectiveness of IVB in patients with nAMD at a tertiary referral center in Indonesia.
Methods: This retrospective study included patients diagnosed with nAMD who received IVB injections at Cipto Mangunkusumo National Referral Hospital between January and December Inclusion criteria encompassed patients with confirmed nAMD and available clinical data pre- and post-injection.
Data on demographics, best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by OCT, and IVB injection regimen were extracted from electronic medical records.
Statistical analysis was performed using Wilcoxon signed-rank and MannAeWhitney U tests, with p < 0.
05 considered statistically significant.
Result: A total of 138 eyes from 131 patients .
ean age: 66.
7 years.
51% mal.
were analyzed.
The median number of injections was three .
ange: 1Ae.
Mean BCVA showed a non-significant improvement from 1.
19 to 1.
14 logMAR .
ean change: 0.
05 logMAR.
p = 0.
Subgroup analysis indicated significant improvement in eyes with baseline VA worse than 1.
32 logMAR .
ean gain: 0.
54 logMAR.
p < 0.
and a significant decline in eyes with baseline VA between 48 and 1.
00 logMAR .
ean loss: 0.
21 logMAR.
p = 0.
CMT significantly decreased by an average of 108.
33 AAm .
< 0.
Conclusion: IVB treatment for nAMD resulted in significant anatomical improvement and was particularly effective in patients with poor baseline visual acuity.
These findings highlight the role of IVB in real-world clinical practice within resource-limited settings.
Keywords: Neovascular age-related macular degeneration, anti-VEGF, intravitreal bevacizumab, visual acuity, central macular thickness Cite This Article: ADRIONO.
Gitalisa Andayani et al.
Real-World Evaluation of the Effectiveness of Intravitreal Bevacizumab Injection for Neovascular Age-Related Macular Degeneration at Cipto Mangunkusumo National Referral Hospital.
International Journal of Retina, [S.
], v.
8, n.
2, p.
165, oct.
ISSN 2614-8536.
Available at: <https://w.
com/index.
php/ijretina/article/view/319>.
Date accessed:
01 oct.
doi: https://doi.
org/10.
35479/ijretina.
Published by: INAVRS https://w.
org/ | International Journal of Retina https://ijretina.
INTRODUCTION
Correspondence to:
Gitalisa Andayani Adriono.
Universitas Indonesia.
Kirana Eye Center - Cipto Mangunkusumo National General Hospital.
Jakarta.
Indonesia, andayani@ui.
Age related macular nAMD With all these factors influencing efficacy, this study aims to evaluate the treatment a leading cause of patterns and therapeutic outcomes of bevacizumab, the most widely available intravitreal anti-VEGF therapy for nAMD patients at a tertiary referral global prevalence of The prevalence of AMD in Asian countries is generally around 3% Ae 19.
2 AMD can be classified into atrophic AMD .
ry or non-exudative AMD) and neovascular AMD .
et AMD).
3,4 In neovascular AMD anti-VEGF degeneration (AMD) is .
AMD), 10Ae13 neovascularization (CNV) play a huge role in impairing visual acuity.
5 Several factors contribute to the development of neovascularization, one of those is vascular endothelial growth factor (VEGF), thus making anti-VEGF as the main treatment of choice for nAMD cases.
Several studies have evaluated the therapeutical effect of anti-VEGF in nAMD, dating to the MARINA and ANCHOR trials where intravitreal anti-VEGF was injected monthly for 24 months and demonstrated the superiority of anti-VEGF therapy.
6 The PrONTO study introduced a more flexible regimen, utilizing an initial loading dose of anti-VEGF for the first three months, followed by a pro re nata (PRN) approach.
Later, subsequent study advocated for the 3-month loading dose followed by a treat-and-extend (TAE) Despite these findings, real-world studies from Europe revealed variability in the implementation of these protocols, with many clinical settings deviating from recommended guidelines.
9 In Indonesia, the first formal guideline for intravitreal anti-VEGF injections including bevacizumab (AVASTIN A) use was introduced in 2012, but adherence was found to be inconsistent among practitioners.
Economic hospital in Indonesia.
METHOD
All nAMD patients who were diagnosed based on clinical examination and macular optical coherence tomography (OCT), and who received intravitreal anti-VEGF bevacizumab injection at the Vitreoretinal Division in Cipto Mangunkusumo National General Hospital from January to December 2017, were included in this retrospective cohort study.
Clinical examinations and OCT assessments were conducted by ophthalmology residents under the supervision of attending vitreoretinal consultants.
Medical records served as the data source for this Records ophthalmology resident to collect demographic and clinical information, including age, gender, laterality of the affected eye, best-corrected visual acuity (BCVA), and central macular thickness (CMT) measured by OCT.
Data were then extracted by fellow authors.
Visual acuity values were converted from the Snellen scale to logarithm of the minimum angle of resolution .
ogMAR).
The number of injections administered, whether the loading dose was completed, and the follow-up interval after the last injection were also recorded.
Patients were excluded if they had incomplete medical records, lacked post-injection examinations, or had received intravitreal agents other than bevacizumab during the study period.
Data extraction was performed by one author and subsequently validated by the other authors to ensure accuracy.
burden in long-term anti-VEGF treatment approach and extensive supporting examinations, patientAos impaired mobility, and mandatory long-term follow up are several determinants which greatly impact the Published by: INAVRS https://w.
org/ | International Journal of Retina https://ijretina.
The bevacizumab injection protocol consisted of incomplete medical records.
A total of 138 eyes from a loading dose of three monthly injections, followed 131 patients were included in the analysis.
The mean by a pro re nata (PRN) regimen.
Reinjection under age of participants was 66.
7 years (SD A 7.
9 year.
, the PRN protocol was determined by the attending with 94% presenting with unilateral nAMD.
The vitreoretinal consultant based on evidence of gender distribution was nearly equal, with 51% male disease activity.
and 49% female.
The mean BCVA prior to injection Statistical analysis was conducted using SPSS
(IBM
MacOS.
1%) having an initial BCVA between Quantitative variables are presented as median 48 and 1.
00 logMAR.
The mean central macular .
or mean .
tandard deviatio.
, depending on thickness (CMT) before injection was 382.
95 AAm (SD the normality of the data, while qualitative variables A 155 AA.
, and the average follow-up duration was 14 months (SD A 3 month.
Corp.
USA)
19 logMAR (SD A 0.
, with the majority of Independent comparisons of categorical data were performed The bevacizumab injection protocol that was using the MannAeWhitney U and FisherAos exact tests.
adapted in this study at the time was a loading dose The Wilcoxon signed-rank test was used for paired administered three times, followed by a PRN sample comparisons.
A p-value of <0.
05 was The median for number of intravitreal considered statistically significant.
bevacizumab injections for our patients within the one-year study period was three injections, ranging RESULTS Our study identified 148 patients who met the inclusion criteria.
however, 17 were excluded due to from one to six injections.
Other demographic and clinical findings of our subjects are listed in Table 1.
Tabel 1.
Demographic and Clinical Data Before Injection .
= .
Age .
7 (SD A 7.
Gender Male 67 .
Female 64 .
Unilateral 124 .
%) Bilateral 7 .
%) Affected eye Average BCVA .
ogMAR (Snellen equivalen.
) 19 .
(SD A 0.
/6 Ae 6/.
>0.
48 Ae 1.
00 (<6/15 Ae 6/.
>1.
00 Ae 1.
32 (<6/60 Ae 3/.
>1.
32 (<3/.
Average CMT 954 (SD .
Average follow up period .
14 (SD .
Number of injections during study period 3 .
Ae .
inimal - maximu.
) Published by: INAVRS https://w.
org/ | International Journal of Retina https://ijretina.
Pre- and post-injection BCVA data were only able to be collected from 93 subjects.
The average BCVA before injection was 1.
19 logMAR .
/60.
SD A 0.
and after injection was 1.
14 logMAR .
/60.
SD A 0.
The mean BCVA change before and after injection was -0.
= 0.
95% CI -0.
13 Ae 0.
Subjects were categorized into 4 categories according to their initial BCVA, and the >0.
48 Ae 1.
00 logMAR range was found to have a significant worsening of visual impairment after injection, reaching an average of 0.
21 logMAR reduction in visual acuity .
= 0.
02, 95% CI 0.
Concurrently, the group with the worst starting BCVA (>1.
32 logMAR) demonstrated a significant 0.
54 logMAR .
< 0.
95% CI -0.
12 Ae 0.
increase in BCVA post-injection.
Changes in BCVA after bevacizumab injection can be observed in Table 2.
Tabel 2.
Change in BCVA .
ogMAR) BCVA pre- Average BCVA Average BCVA pre-injection post-injection Average BCVA Number .
ogMAR .
ogMAR .
ogMAR) of eyes (Snelle.
) (Snelle.
) .
ogMAR) 95% CI 0 - 0.
/7.
40 Ae 0.
>0.
48 - 1.
04 Ae 0.
>1.
00 - 1.
44 Ae 0.
>1.
<0.
83 Ae -0.
In this study, post-injection central macular thickness data was garnered from 115 subjects.
In general, a significant reduction in central macular thickness was shown in this study, with a mean change of 108.
33 AAm .
< 0.
95% CI 75.
5 Ae 141.
A detailed analysis of each group suggested that the group with the best starting BCVA before injection .
Ae 0.
48 logMAR) exhibited the greatest improvement in central macular thickness .
76 AAm.
p = 0.
95% CI 11.
82 Ae 201.
A significant change in central macular thickness was also observed in the worst initial BCVA group .
50 AAm.
p < 0.
95% CI 109 Ae .
Other data regarding the change in central macular thickness can be seen in Table 3.
Tabel 3.
Change in central macular thickness Average Average central
Average central
BCVA
Number thickness pre- thickness post- .
ogMAR) of eyes 95% CI All eyes <0.
5 Ae 141.
0 - 0.
8 Ae 201.
>0.
48 - 1.
<0.
10 Ae 83.
>1.
00 - 1.
12 Ae 182.
>1.
<0.
109 Ae 254 Published by: INAVRS https://w.
org/ | International Journal of Retina https://ijretina.
Our study also did a subgroup analysis on the change of BCVA while grouping our subjects based on their therapy regimen, complete or incomplete loading dose.
Sixty-five subjects were a part of the complete loading dose group, while 28 subjects were categorized into the incomplete loading dose group.
Our study suggested a statistically significant BCVA improvement within the complete loading dose group (-0.
05 logMAR.
p = 0.
95% CI -0.
186 Ae -0.
, whereas the incomplete loading dose group underwent worsening of visual acuity, though the result was not statistically significant .
= 0.
95% CI -0.
19 Ae -0.
Table 4 depicts the association between intravitreal bevacizumab dose on patientAos visual outcome.
Tabel 4.
Change in BCVA .
ogMAR), grouped by injection dose Complete loading dose Incomplete loading dose Number of Average change in BCVA .
ogMAR) 95% CI 186 Ae -0.
19 Ae 0.
Seventy-seven subjects were followed up equal to or more than 6 months, and 16 subjects were followed up no later than 6 months.
Subjects in both groups experienced changes in visual acuity.
The group with a follow up period of equal to or more than 6 months experienced improved visual acuity, while those who underwent an average follow up period of less than 6 months experienced worsening visual acuity.
However, changes in visual acuity in both groups did not reach statistical significance (Table .
Tabel 5.
Change in BCVA .
ogMAR), grouped by mean follow up duration after last intervention Number of Average change in BCVA .
ogMAR) 95% CI 20 - 1.
Less than 6 months 05 - 0.
Equal to or more than 6
DISCUSSION