The effect of real-world follow up delay between planned intravitreal anti-VEGF treatments for neovascular age- related macular degeneration on retinal thickness

doi:10.21203/rs.3.rs-2584504/v1

Download PDF

Research Article

The effect of real-world follow up delay between planned intravitreal anti-VEGF treatments for neovascular age- related macular degeneration on retinal thickness

https://doi.org/10.21203/rs.3.rs-2584504/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Purpose: To study the impact of real-world follow-up delay on anatomical outcomes for age-related macular degeneration (AMD) treated with intravitreal injection.

Methods: A retrospective, sequential, observational cohort analysis of the Whangārei Hospital retinal clinic was conducted between Aug 2021 – Dec 2021. Planned follow-up time on treat and extend (T&E) protocol was compared with actual follow-up injection time. OCT Central Subfield Thickness (CST) measurements were compared between treatment reviews for each patient.

Results: The mean delay from planned injection for patients receiving intravitreal injection (n=709) was 6.51 days [SD = 13.88]. Eyes that received an intravitreal injection within 7 days of their planned treatment date prior to clinical review (n=209) had a mean reduction of their CST [-5.74mm ± 2.84mm]. Eyes that received treatment later than 7 days from their planned treatment date prior to clinical review (n=152) had a mean increase in the CST [9.03mm ± 4.33mm]. We established a time-dependent correlation between increased delay (in weeks) and CST.

Conclusion: A delay greater than 7 days from planned injection was associated with a statistically significant increase in the CST in patients with AMD. It also indicates the importance of adherence to recommended follow-up timeframes when following T&E protocol.

Neovascular age-related macular degeneration

intravitreal injections

delayed follow-up visit

Age-related macular degeneration (AMD) the leading cause of severe vision loss in individuals over the age of 50 years [1]. AMD is a chronic, progressive disease that affects approximately 200 million people, 8.7% of the world population and contributes to 16.5% of blindness in Australasia [1–3]. The prevalence of AMD is set to increase; affecting over 200,000 people, accounting for 12.9% of New Zealand’s population [4].

Neovascular AMD (nAMD) is characterised by retinal pigment epithelium dysfunction and associated choroidal neovascularisation (CNV) [5]. Leakage of intraretinal and subretinal fluid, as well as pigment epithelial detachments results in rapid vision loss [5]. nAMD is commonly treated with intravitreal anti-VEGF agents with the aim of reducing intraretinal and/or subretinal fluid exudation. The injection interval plays a significant role in the time for choroidal neovascular lesions to become inactive and delay can cause vision loss [6–8]. Intravitreal injections of Anti-VEGF are generally given at 4 week intervals, with initial studies showing an improvement in BCVA over the first three months before plateauing [9, 10]. As a result, 3 successive monthly treatments are accepted as a loading protocol [11, 12]. Most current anti-VEGF agents have effective action for 4–6 weeks. [13] After the loading phase, treat and extend (T&E) protocols are designed to reduce the burden of frequent patient assessments and unnecessary treatment [11, 12]. Although adherence to these regimens has been shown to slow vision loss in nAMD, there has been limited assessment of the implications of deviation from intended treatment intervals.

Optical coherence tomography (OCT) is a light-wave based imaging modality that allows high-definition cross-sectional imaging of the retina and deeper tissues [14]. OCT has been well established as a diagnostic and monitoring tool in the management of nAMD [15]. Fourier-domain OCT (SD-OCT) has been demonstrated to have high repeatability for macular and central subfield thicknesses [16–19]. Increased foveal thickness in nAMD is often due to the presence of intraretinal or subretinal fluid [20].

Deviation from treatment plans may have significant implications for the stability of visual function. Delay > 4 weeks of anti-VEGF treatment of nAMD has been shown to result in significant anatomical and visual compromise that does not completely resolve upon retreatment [21]. The impact on treatment lapse on functional and anatomical outcomes has recently come to attention in nAMD, partly due to the COVID-19 pandemic.

This study aimed to assess the impact of treatment delay on the retinal morphology and functional outcomes of patients with nAMD using real-world data.

Study Design

We analysed retrospective data for eyes treated with intravitreal injections of anti-VEGF agents for the treatment of nAMD in the Ophthalmology Department in Whangarei Hospital, New Zealand. The research proposal was reviewed by HDEC and deemed to be out of scope for NZ Ethics Approval. The Local Audit and Research Assessment committee and Chief Medical Officer at Whangarei Hospital also evaluated the study and deemed it not to require ethics approval and waived informed consent given its retrospective nature. The research described adhered to the principles of the Declaration of Helsinki. Data were obtained for clinical visits to the medical retinal service from 16 August through 31 December 2021. All patients had been previously assessed by a clinician as having nAMD appropriate for treatment with anti-VEGF therapy. Treatment decisions were solely clinician choices and made as part of routine clinical practice. Injections were delivered according to the Whangarei Hospital intravitreal injection protocol and part of a T&E protocol.

Patient Selection and Data Collection

Each eye was included as a separate injection event when patients required bilateral treatment. Inclusion criteria for analysis were patients who received anti-VEGF injections for nAMD. Exclusion criteria were < 50 years of age, other retinal comorbidities, poor or missing OCT scan data (graded as 5/10 or less by Zeiss Cirrus software) and those who had received intravitreal injection outside of Northland DHB services during the study. Injections with delay > 3 months were also excluded as ‘lost to follow-up’. Variables collected included patient demographics, pinhole visual acuity (VA) at assessment visits, medication used, OCT data and treatment plan information. Treatment plans were categorized by the number of treatments planned in a series of injections. The stage of treatment was defined as which injection within that series was being delivered (i.e., 1 of 3). The clinician-requested interval between each clinical visit was also recorded.

At each assessment visit, OCT CST was compared to measurements obtained at the last clinical visit, provided this was within 3 months, resulting in a CST change (Δ) measurement. All patients were imaged using the Zeiss Cirrus HD-OCT 5000 OCT system with 512x128 macular scans and Cirrus OCT software was used to determine the central subfield thickness (CST) of the central disc 1mm in diameter centred on the fovea. The CST was defined as the sum of the thickness of the central neurosensory retina including intraretinal fluid, and the height of the subretinal fluid, calculated using segmentation mapping [22, 23]. Pinhole visual acuity (VA) was measured at each assessment clinic visit using an EDTRS chart under standard conditions [24]. Pinhole Snellen values were converted to LogMAR using the formula provided by Tiew et al. [25].

Data and Statistical Analysis

Statistical analysis was performed in Excel v16.62 (Microsoft Corp., Richmond, WA) and SPSS v29.0 (IBM Corp. Armonk, NY). Descriptive statistics included mean, standard deviation, 95% confidence intervals (CIs). A measurement correction of ±11.6µm obtained from the Cirrus HD-OCT user manual repeatability standard deviation appendix (specific to AMD) was applied to each CST Δ value. CST Δ values were graded. Values indicating an increase in thickness were assigned a total change value (TCV) of 1. Values indicating a decrease in thickness were assigned a TCV of -1. Values that fell between the repeatability standard deviation (±11.6µm) from 0 (no change) were assigned a TCV of 0. This calculation was applied to distinguish patients that likely had no meaningful change in CST that would influence the decision to change a treatment plan. Normality tests were applied to the data and appropriate parametric/non-parametric testing including Welch’s t-test and Pearson’s chi-squared tests were subsequently employed. Statistical significance set at 𝛂 = 0.05.

Primary Outcome

The primary outcome measurement was mean CST change within 1 week of the requested treatment date. This was compared with the mean CST change for injections occurring more than 1 week later than the requested treatment date.

Secondary Outcomes

Subgroup analysis including individual week groups by delay were conducted. TCV values were calculated and compared for all pre-assessment injections and compared. LogMAR visual acuity change (VA Δ) was also evaluated as part of the secondary analysis.

Population characteristics

Table 1.0 Standard deviation (SD)

		nAMD (n = 251)
Population Characteristics		No. (%)	Mean (± SD)
Female		146 (58.2)	-
Age, years		-	81.2 (7.6)
< 70		20 (7.9)	-
70–80		89 (35.3)	-
> 80		142(56.6)	-
Bilateral injections		45 (17.9)	-
Ethnicity
NZ European		199 (79.3)	-
NZ Māori		9 (3.6)	-
Other European		40 (15.9)	-
Latin American		1 (< 1)	-
Pacific Islander		1 (< 1)	-
Middle Eastern		1 (< 1)	-
	nAMD (n = 709)
Injection Characteristics	No. (%)
Right Eyes	319 (44.9)
Bilateral Injections	103 (14.5)
Medication Used
Bevacizumab	370 (52.2)
Ranibizumab	334 (47.1)
Aflibercept	5 (< 1)
Series Information
1st in series	204 (28.8)
2nd in series	240 (33.9)
3rd in series	260 (36.7)
4th in series	5 (< 1)

For nAMD treatments, 709 injections were completed in 296 eyes, for 251 patients. The mean (± SD) age of patients at the time of injection was 81.2 ± 7.61 years (range 60–97) and 58.2% of patients were female. 79.3% of patients were identified as NZ European by their national health index demographic data. Further demographics are summarised in Table 1.0. Injection characteristics are summarised in table 2.0.

Table 2.0. Standard deviation (SD)

Interval Requested (Weeks)	n	Mean Delay (SD)
4	289	6.31 (13.75)
5	32	6.00 (14.86)
6	180	5.42 (12.32)
7	23	4.70 (15.35)
8	110	9.86 (26.06)
9	3	3.67 (14.74)
10	28	8.04 (20.48)
11	1	8.00 (NA)
12	25	10.76 (14.15)

Delay and Follow-Up Data

398 injections were the first in a requested series of treatments and were included in the anatomical statistical analysis. 3 injections were excluded as ‘lost to follow-up’ and 25 were excluded for inadequate OCT imaging or documentation. This left a total of 370 follow-up injections eligible for anatomical statistical analysis.

The median follow-up delay for all nAMD treatments was 2 days (IQR 0 to 8) from the requested date. 36.6% of cases were treated on or before the recommended date (n = 260). 31.5% of cases were treated between 1 and 6 days as requested (n = 223). A delay in treatment ≥ 7 days from the requested date occurred in 31.8% of cases (n = 223). Of those treated ≥ 7 days from the requested date, the median delay was 13 days (IQR Q1 to Q3: 8 to 23).

Anatomical Outcomes

Eyes that received an intravitreal injection within 7 days of their requested injection date (n = 209) had a mean CST change of -5.74µm ± 2.85µm. Those receiving injections after 7 days from their requested injection date (n = 152) had a mean CST change of 9.03µm ± 4.33µm. There was a significant association between intravitreal injection delay and increased retinal thickness (Welch’s T-test p = 0.0043). Of injections completed within 7 days of the requested date, 28% had an interval decrease in the CST, 17% had interval increase and 55% were stable within ± 11.6µm. Of injections completed later than 1 week, 13% saw an interval decrease in CST, 40% saw an increase and 47% were stable. Subgroup analysis by week-group delay showed a delay-dependent increase in the CST. (Fig. 1.0).

Anatomical outcomes were categorised as better, no change (0±11.6µm) or worse. Each outcome was coded as an integer (total change value, TCV). Patients that received an intravitreal injection within 7 days of their requested injection date had a mean TCV of -0.11 (SD = 0.66) indicating improvement. Those receiving injections later than 7 days of their requested injection date had a mean TCV of 0.27 (SD = 0.68) indicating deterioration. There was a statistically significant difference between the means of these groups (p = < 0.001).

Table 3.0. Distribution of requested intervals > 4 weeks. The Kruskal-Wallis Test of difference between groups significance p = 0.249 at a significance level of 0.05 indicating no significant difference between groups. Standard deviation (SD).

	Treatment Delay (days)
nAMD	<⁻8	⁻7 - ⁻1	0–6	7–13	14–20	21–27	> 28
Count	9	55	154	64	31	16	41
TCV Thinner (%)	33.3	34.5	26.0	15.6	9.7	6.3	14.6
TCV No Change (%)	55.6	49.1	57.1	51.6	51.6	43.8	41.5
TCV Thicker (%)	11.1	16.4	16.9	32.8	38.7	50.0	43.9
Mean TCV (SD)	-0.22 (0.67)	-0.18 (0.69)	-0.09 (0.65)	0.17 (0.68)	0.29 (0.64)	0.44 (0.63)	0.33 (0.71)
Mean CST Δ (SD)	-5.78 (52.83)	-11.91 (50.18)	-3.54 (37.41)	3.33 (60.86)	4.10 (16.84)	15.06 (19.84)	19.53 (67.09)
Median CST Δ (IQR)	-7.00 (-20 to 6)	-2.00 (-15.5 to 2)	0.10 (-12.5 to 6)	3.00 (-5.25 to 17)	3.00 (-6 to 13.5)	10.50 (-2.25 to 29.8)	9.00 (-4 to 35)

Visual Acuity and Other Secondary Outcomes

Complete visual acuity data was available for 302 eyes with complete OCT data (81.6%). 169 eyes received an intravitreal treatment within 1 week of the requested injection date and had a mean VA improvement of 0.0031 LogMAR (SD = 0.18). 128 eyes received injections later than 1 week of the requested injection date had a mean VA loss of 0.030 LogMAR (SD = 0.16). The difference between the groups was not significant. There was no significant VA change pattern found when individual week groups were assessed. No correlation was found between delay times, the medication used or age at injection.

COVID-19 created significant disruption to healthcare worldwide, with unavoidable, unpredictable and intermittent delays. The COVID-19 pandemic resulted in significant international disruption in the treatment of nAMD and reports of real-world delay occurred in up to 50% of planned injections [26–28]. New Zealand enjoyed a relatively low burden of disease from the pandemic; however, this came at the expense of restrictive lockdown policy. The Royal New Zealand and Australian College of Ophthalmologists released updated branch triage guidelines to prioritise nAMD treatment [29]. This situation provided an opportunity to study the impact of treatment delay in nAMD using real-world data, focusing on non-adherence outcomes. Non-adherence is influenced by multiple factors including healthcare access, disease impact, treatment side effects, patient-related factors and socioeconomic factors [30].

Our retrospective review of Northland DHB injection delay for patients with AMD showed a median delay of 2 days from the requested date with a delay > 1 week occurring in 31.8% of injections. This delay was shorter than other international audits of injection delay practices during this time [31, 32]. Delay to injection did not correlate well with lockdown periods, possibly due to the success of prioritization guidelines.

Our data shows a time-dependent increase in central macular thickness occurs in active disease that is not treated within a week of requested date when following a T&E protocol. Delay to initial injection from the time of diagnosis is correlated with reduced visual recovery at 6 months [33]. Teo et al. showed that delayed retreatment of active disease resulted in poorer visual outcomes, whereas timely treatment was associated with better 12-month vision and reduced CST [34]. This has been proposed to be due to the accumulation of irreversible structural changes in the macula, leading to an inability to recover functional vision with treatment.

The data suggest that the accumulation of these changes is progressive and associated with time spent with active CNV without sufficient anti-VEGF cover. Structural changes in active disease occur over days, resulting in significant differences between timely and delayed injection outcomes. Our data suggest deterioration in visual acuity after a week’s delay; however, the difference between groups was statistically insignificant. The disparity between functional and anatomical outcomes may have been due to short measurement intervals failing to detect the impact of macular thickness changes and photoreceptor loss.

Limitations

The mean LogMAR change was equivalent to more than a letter of acuity loss when injections were delayed further than one week from requested interval, however the difference between groups was not statistically significant. Further analysis with a larger sample population may help further elucidate the functional impacts of delay. Secondly, assessment of the true impact of the COVID-19 lockdown period on delay times was challenging due to the fluctuant nature of the restrictions. Lastly, the only biomarker commonly used in T&E assessments that was examined in our study was OCT CST. There is conflicting evidence as to whether foveal thickness at baseline is a predictor for functional improvement although is a commonly used marker for treatment decision change [35].

In conclusion, our data provides insight into a ‘safe window’ of injection of ±7 days from the requested injection date, that may allow health providers to optimize on-time treatment. Further research into the functional and anatomical consequences of intravitreal injection delay is required to help guide the evolution of nAMD treatment regimens as we continue to rely on current anti-VEGF agents.

Conflicts of Interest

The author was employed by Te Whatu Ora Health New Zealand Te Tai Tokerau during the course of research

Funding

No funding was sought or gained in relation to this article

Availability of Data: Available upon request

Funding

The authors gathered and interpreted data while being employees of Northland District Health Board (now Te Whatu Ora Health New Zealand Te Tai Tokerau) and Te Whatu Ora Health New Zealand Auckland. The authors declare that no funds, grants or other support were received with respect to the preparation of this manuscript.

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Author Contribution

Research Design (James Corbett, Andrew Watts), Data Acquisition (James Corbett), Data Analysis (James Corbett), Manuscript Preparation (James Corbett, Andrew Watts, Francesc March de Ribot, Rachael Niederer).

Ethics Approval

The research proposal was reviewed by HDEC and deemed to be out of scope for NZ Ethics Approval. The Local Audit and Research Assessment committee and Chief Medical Officer at Whangarei Hospital also evaluated the study and deemed it not to require ethics approval and waived informed consent given its retrospective nature.

Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global Health 2014;2(2):e106-e16.
Flaxman SR, Bourne RR, Resnikoff S, et al. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. The Lancet Global Health 2017;5(12):e1221-e34.
Age-related Macular Degeneration. Wellington: National Health Committee. 2015. Available from: http://www.nhc.health.govt.nz
Worsley D, Worsley A. Prevalence predictions for age-related macular degeneration in New Zealand have implications for provision of healthcare services. The New Zealand Medical Journal (Online) 2015;128(1409):44.
Hallak JA, de Sisternes L, Osborne A, et al. Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmology 2019;137(7):738–44.
Gillies MC, Campain A, Walton R, et al. Time to initial clinician-reported inactivation of neovascular age-related macular degeneration treated primarily with ranibizumab. Ophthalmology 2015;122(3):589–94. e1.
Greenlee TE, Wang VY, Kang H, et al. Consequences of lapses in treatment with Vascular Endothelial Growth Factor Inhibitors in Neovascular Age-related Macular Degeneration in Routine Clinical Practice. Retina 2021;41(3):581–7.
Ramakrishnan MS, Yu Y, VanderBeek BL. Association of Visit Adherence and Visual Acuity in Patients With Neovascular Age-Related Macular Degeneration: Secondary Analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial. JAMA Ophthalmology 2020;138(3):237–42.
Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. American journal of ophthalmology 2007;143(4):566–83. e2.
Gupta OP, Shienbaum G, Patel AH, et al. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration: clinical and economic impact. Ophthalmology 2010;117(11):2134–40.
Kertes PJ, Galic IJ, Greve M, et al. Efficacy of a treat-and-extend regimen with ranibizumab in patients with neovascular age-related macular disease: a randomized clinical trial. JAMA ophthalmology 2020;138(3):244–50.
Guymer RH, Markey CM, McAllister IL, et al. Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen: FLUID study 24-month results. Ophthalmology 2019;126(5):723–34.
Fauser S, Muether PS. Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. British Journal of Ophthalmology 2016;100(11):1494–8.
Castillo MM, Mowatt G, Elders A, et al. Optical coherence tomography for the monitoring of neovascular age-related macular degeneration: a systematic review. Ophthalmology 2015;122(2):399–406.
Schmidt-Erfurth U, Klimscha S, Waldstein SM, Bogunović H. A view of the current and future role of optical coherence tomography in the management of age-related macular degeneration. Eye 2017;31(1):26–44.
Parravano M, Oddone F, Boccassini B, et al. Reproducibility of Macular Thickness Measurements Using Cirrus SD-OCT in Neovascular Age-Related Macular Degeneration. Investigative Ophthalmology & Visual Science 2010;51(9):4788–91.
Wolf-Schnurrbusch UE, Ceklic L, Brinkmann CK, et al. Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments. Investigative ophthalmology & visual science 2009;50(7):3432–7.
Huang J, Liu X, Wu Z, et al. Macular and retinal nerve fiber layer thickness measurements in normal eyes with the Stratus OCT, the Cirrus HD-OCT, and the Topcon 3D OCT-1000. Journal of glaucoma 2011;20(2):118–25.
Odell D, Dubis AM, Lever JF, et al. Assessing Errors Inherent in OCT-Derived Macular Thickness Maps. Journal of Ophthalmology 2011;2011:692574.
Jaffe GJ, Martin DF, Toth CA, et al. Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials. Ophthalmology 2013;120(9):1860–70.
Yalamanchili SP, Maatouk CM, Enwere DU, et al. The Short-term Effect of a Single Lapse in Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema Within Routine Clinical Practice. American journal of ophthalmology 2020;219:215–21.
Mylonas G, Ahlers C, Malamos P, et al. Comparison of retinal thickness measurements and segmentation performance of four different spectral and time domain OCT devices in neovascular age-related macular degeneration. British Journal of Ophthalmology 2009;93(11):1453–60.
Keane PA, Mand PS, Liakopoulos S, et al. Accuracy of retinal thickness measurements obtained with Cirrus optical coherence tomography. British Journal of Ophthalmology 2009;93(11):1461–7.
Ramachandran N, Sanderson G, Bevin TH, Wynn-Williams G. Accuracy of visual acuity testing in New Zealand primary health care. NZ Med. J. 2013;126:78–88.
Tiew S, Lim C, Sivagnanasithiyar T. Using an excel spreadsheet to convert Snellen visual acuity to LogMAR visual acuity. Eye 2020;34(11):2148–9.
Wasser LM, Weill Y, Brosh K, et al. The impact of COVID-19 on intravitreal injection compliance. SN Comprehensive Clinical Medicine 2020;2(12):2546–9.
Viola F, Milella P, Giuffrida FP, et al. Impact of coronavirus disease pandemic on intravitreal injections treatment for macular diseases: Report from a referral hospital in Milan. Retina 2021;41(4):701–5.
Xu D, Starr MR, Boucher N, et al. Real-world vitreoretinal practice patterns during the 2020 COVID-19 pandemic: a nationwide, aggregated health record analysis. Current opinion in ophthalmology 2020;31(5):427–34.
Anon. RANZCO COVID-19 Triage Guidelines. 2020. Available from: https://ranzco.edu/policies_and_guideli/ranzco-covid-19-triage-guidelines/
Sobolewska B, Sabsabi M, Ziemssen F. Importance of Treatment Duration: Unmasking Barriers and Discovering the Reasons for Undertreatment of Anti-VEGF Agents in Neovascular Age-Related Macular Degeneration. Clinical ophthalmology (Auckland, N.Z.) 2021;15:4317–26.
Navarrete A, Vofo B, Matos K, et al. The detrimental effects of delayed intravitreal anti-VEGF therapy for treating retinal pathology: lessons from a forced test-case. Graefe's Archive for Clinical and Experimental Ophthalmology 2022:1–8.
Hurand V, Ducloyer JB, Baudin F, et al. IMPACT study: Impact of adherence to anti-VEGF intravitreal injections for macular disease during COVID 19‐related confinement in France. Acta ophthalmologica 2022.
Lim JH, Wickremasinghe SS, Xie J, et al. Delay to treatment and visual outcomes in patients treated with anti-vascular endothelial growth factor for age-related macular degeneration. American journal of ophthalmology 2012;153(4):678 – 86.e6862.
Teo KYC, Saxena N, Gan A, et al. Detrimental effect of delayed re-treatment of active disease on outcomes in neovascular age-related macular degeneration: the RAMPS study. Ophthalmology Retina 2020;4(9):871–80.
Claessens D, Schuster AK. Correlation of quantitative metamorphopsia measurement and central retinal thickness in diabetic macular edema and age-related exsudative macular degeneration. Klinische Monatsblatter fur Augenheilkunde 2018;236(7):877–84.
Statements & Declarations

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

The effect of real-world follow up delay between planned intravitreal anti-VEGF treatments for neovascular age- related macular degeneration on retinal thickness

Status:

Version 1

Abstract

Figures

Introduction

Methods

Study Design

Patient Selection and Data Collection

Data and Statistical Analysis

Primary Outcome

Secondary Outcomes

Results

Population characteristics

Delay and Follow-Up Data

Anatomical Outcomes

Visual Acuity and Other Secondary Outcomes

Discussion

Limitations

Declarations

References

Additional Declarations

Status:

Version 1