Implantable miniature telescope (IMT) for vision loss due to end-stage age-related macular degeneration

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effectiveness of the IMT in improving visual acuity and safety in people with late or advanced AMD. An additional primary objective will be to assess the device's effects on QoL.

Background

Description of the condition

Age-related macular degeneration (AMD) is an age-associated disease that causes progressive and irreversible damage to the central part of the retina (macula), resulting in loss of central vision (National Eye Institute 2012). While the exact cause of AMD is unknown, risk factors include increased age, family history, smoking, hypertension, and increased sun exposure (AAO 2013).

AMD has two forms and is diagnosed as either dry (non-neovascular) or wet (neovascular). Dry AMD is more prevalent than the wet form, and is responsible for approximately 90% of cases (Ferris 1984). Both forms can progress to advanced-stage AMD and are associated with severe disability (Bennion 2012). In advanced dry AMD, central vision loss is caused by the breakdown of the light-sensitive cells in the macula (cones), which causes a blurry or blank spot to develop in the visual field (geographic atrophy). This spot can advance in size, further accelerating vision loss. In advanced wet AMD, central vision loss is caused by the growth of bleeding and leaking blood vessels that have grown under the macula (National Eye Institute 2012).

AMD is the third leading cause of irreversible visual impairment worldwide and the leading cause of blindness in industrialized countries (World Health Organization 2012). In the US, AMD affects 1.75 million people (Friedman 2004). Since AMD prevalence rises with age, the number of cases worldwide is expected to increase as the population ages (Rein 2009).

Description of the intervention

The implantable miniature telescope (IMT) is an ophthalmic device that works in conjunction with the cornea to improve near and distance vision in individuals who have lost central vision due to bilateral, wet or dry, end-stage AMD (FDA 2010). Once implanted, the telescope enlarges objects in the person's central visual field and focuses them onto healthy areas of the retina not affected by AMD, allowing individuals to recognize objects that they could not otherwise see with their natural lens (Hudson 2006). The telescope is implanted monocularly and eliminates peripheral vision in the eye in which it is implanted. As a result, the individual must rely solely on the nonimplanted eye for peripheral vision after surgery (Hudson 2006).

The IMT is manufactured by VisionCare Ophthalmic Technologies (Saratoga, CA). The device received FDA approval in 2010 (FDA 2010). It is the only implantable telescope commercially available for treatment of end-stage AMD. The IMT is 4.4 mm long and 3.6 mm in diameter. It weighs 115 mg in air and 60 mg in aqueous humor. There are two IMT models, the WA (wide-angle) 2.2X and the WA 3.0X (FDA 2010).

How the intervention might work

The IMT is monocularly implanted by ophthalmic surgeons in an outpatient procedure under local anesthesia. The telescope is placed behind the pupil in the posterior chamber of the eye after the cataractous crystalline lens has been removed. The device is held in position by haptic loops. No intraocular lens is used in conjunction with the device (Lane 2004). Surgical preparation, surgery, and recovery take approximately two to three hours (VisionCare 2010).

The US Food and Drug Administration (FDA) has determined that the IMT is indicated in people with the following (FDA 2009):

  • age 75 years or older with stable, moderate to profound central vision impairment caused by end-stage AMD;

  • retinal findings of geographic atrophy or disciform scar with foveal involvement;

  • evidence of cataract (unilateral), but no previous cataract surgery;

  • agreement to undergo training with an external telescope prior to surgery to determine whether adequate vision can be obtained (two to four sessions);

  • achieve at least a five-letter improvement on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart with an external telescope;

  • adequate peripheral vision in eye not scheduled for surgery;

  • willingness to participate in postoperative visual training program.

Why it is important to do this review

AMD causes loss of central vision, which is needed for daily activities such as recognizing faces, reading, and driving (Lane 2004). Individuals with AMD experience high levels of emotional distress and reductions in key aspects of quality of life (QoL) (Williams 1998). Financial costs associated with visual impairment are considerable, and include medical care, loss of income, and paid home help (Mitchell 2006). Currently, there are no effective treatments for advanced, dry AMD (National Eye Institute 2012). For wet AMD, options for preventing disease progression include laser surgery, photodynamic therapy, and anti-vascular endothelial growth factor (VEGF) injections. However, there are no surgical treatments for improving visual acuity (Hudson 2006). The heavy burden of the disease, the expected increase in the number of cases, and the current lack of effective alternatives underscore the need to examine new treatment options (Gehlbach 2012).

Objectives

To assess the effectiveness of the IMT in improving visual acuity and safety in people with late or advanced AMD. An additional primary objective will be to assess the device's effects on QoL.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomized controlled trials (RCTs). We will include trials that compared baseline visual acuity in the study eye with postsurgical visual acuity in participants randomized to receive the IMT and in participants not randomized to the IMT.

If the desired types of studies are not available, we will consider including randomized within-person study designs that compared baseline visual acuity with postsurgical visual acuity between eyes randomized to receive the IMT and fellow eyes not receiving the IMT. We also will consider quasi-RCTs if no RCTs are found.

Types of participants

We will include trials that recruited participants with late/advanced or end-stage bilateral wet or dry AMD with central vision loss. We will define late/advanced and end-stage AMD as retinal findings of geographic atrophy or disciform scar with foveal involvement.

Types of interventions

The intervention is the IMT, including both models, 2.2X and 3.0X. We will assess each model separately against no treatment (no IMT).

Types of outcome measures

Primary outcomes
Primary outcomes for the comparison of treatments
  1. The proportion of participants who gain 2 or more lines of best-corrected distance visual acuity (BCVA) (logMAR or equivalent) in the study eye 12 months after surgery (or study enrollment).

  2. Change in QoL measured as the difference in QoL from baseline (time of IMT implantation) to 12 months following surgery (or study enrollment). QoL will be assessed as a continuous variable using the Activity of Daily Living Scale Questionnaire, the National Eye Institute Visual Functioning Questionnaire, or any other validated QoL instrument.

Secondary outcomes
Secondary outcomes for the comparison of treatments
  1. The proportion of participants who gain 2 or more lines of BCVA (logMAR or equivalent) in the study eye six and 18 months after surgery (or study enrollment).

  2. Change in QoL from baseline (time of IMT implantation) to six and 18 months following surgery (or study enrollment).

  3. Mean change in BCVA (logMAR or equivalent) from baseline (time of IMT implantation) to six, 12, and 18 months following surgery (or study enrollment).

  4. The proportion of participants who lose 2 or more lines of BCVA (logMAR or equivalent) in the study eye six, 12, and 18 months after surgery (or study enrollment).

Adverse effects and surgical complications

Since the IMT is implanted monocularly, the following adverse effects and surgical complications can only occur in the eye receiving the intervention. We will provide a narrative summary when possible for the following events in eyes receiving the implant.

  1. The proportion of eyes with aborted surgery.

  2. The proportion of eyes with device explantation.

  3. The proportion of participants with BCVA 20/200 or worse in the study eye six, 12, and 18 months after surgery (or study enrollment).

  4. The mean endothelial cell density (ECD) loss at 12 or more months after surgery. Due to the length of the IMT, it protrudes into the anterior chamber when implanted, and implantation can lead to loss of endothelial cells and diminished ECD. These cells are essential for maintaining the clarity of the cornea. We will report the mean ECD loss as a proxy measure to assess risk of corneal transplant. Mean ECD loss will be measured as the change in ECD from baseline to 12 or more months following surgery among eyes that receive the implant.

Additional outcomes of importance to participants

We will provide a narrative summary when possible for the following.

  1. Proportion of participants undergoing IMT surgery who have difficulty adjusting to loss of peripheral vision in treated eye, as reported by investigators.

  2. Proportion of participants undergoing IMT surgery with postoperative pain.

  3. Healing time following IMT surgery.

Search methods for identification of studies

Electronic searches

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (latest issue), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to present), EMBASE (January 1980 to present), PubMed (1966 to present), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to present), the Allied and Complimentary Medicine Database (AMED) (January 1985 to present), Web of Science Conference Proceedings Citation Index-Science (CPCI-S) (January 1970 to present), System for Information on Grey Literature in Europe (OpenSIGLE), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), World Health Organization International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/en/) and the US Food and Drug Administration (FDA) Medical Devices (www.fda.gov/MedicalDevices/). We will not use any date or language restrictions in the electronic search for trials. 

See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), PubMed (Appendix 4), LILACS (Appendix 5), AMED (Appendix 6), CPCI-S (Appendix 7), OpenSIGLE (Appendix 8), mRCT (Appendix 9), ClinicalTrials.gov (Appendix 10), ICTRP (Appendix 11) and the FDA (Appendix 12).

Searching other resources

We will search the reference lists of potentially relevant studies to identify any further additional trials. We will not handsearch journals or conference proceedings specifically for this review.

Data collection and analysis

Selection of studies

Two review authors (AG and JL) will independently evaluate all titles and abstracts obtained from the searches. We will classify each record as definitely relevant, possibly relevant, or definitely not relevant. We will obtain full-text reports of records classified as definitely relevant or possibly relevant by both review authors. Two review authors will independently review the full-text reports to determine final inclusion status. Papers that are excluded after full-text evaluation will be described in the 'Characteristics of excluded studies' table with reasons for exclusion. We will resolve discrepancies at all stages by discussion. In any case where agreement between AG and JL regarding inclusion or exclusion status is not reached, a third review author (MK) will assist in making the final decision. For studies written in languages not read by the review authors, we will identify colleagues to assist with assessing the eligibility and, when needed, to translate the report for further review.

Data extraction and management

Two review authors (AG and JL) will independently extract data from all included studies using data abstraction forms developed by the Cochrane Eyes and Vision Group. We will compare results and resolve discrepancies by discussion between both review authors, referring back to the original article when necessary. When data are not available in the published report for primary or secondary outcomes of interest, we will contact the study authors and request for relevant data in an effort to overcome any selective reporting biases. We will allow the authors four weeks to respond. When necessary, we will extract data from figures in the reports and contact the study authors to confirm or refute the accuracy of data so obtained and will perform sensitivity analyses to determine the impact of using data extracted from figures. In cases where agreement is not reached between review authors (AG and JL), a third review author (MK) will assist in decision-making. One review author will enter all data into Review Manager 5 (RevMan 2012), and a second review author will verify these data.

Assessment of risk of bias in included studies

Two review authors (AG and JL) will independently assess the risk of bias of each trial and any disagreement will be resolved by discussion. We will use Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions to guide the assessment of the risk of bias of each trial included in the review (Higgins 2011). The two review authors will consider the following for each trial.

  1. Sequence generation (selection bias).

  2. Allocation concealment (selection bias).

  3. Masking (blinding) of study personnel (performance bias).

  4. Masking of outcome assessors (detection bias).

  5. Incomplete outcome data (attrition bias).

  6. Selective outcome reporting (reporting bias).

  7. Other biases.

We will assess each risk of bias domain as 'low risk of bias', 'high risk of bias', or 'unclear' for each trial. Since there may be variation in the risk of bias among different outcomes within a study, we will assess the risk of bias at the level of outcomes rather than for the entire study when appropriate (i.e. for Masking of outcomes assessors and Incomplete outcome data). If quasi-randomized studies are included, we will consider these types of studies to be at high risk of selection bias due to inadequate sequence generation and unlikelihood of allocation concealment as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If we detect other types of bias, such as source of funding or conflict of interest, we will present these. We will discuss the potential impacts on treatment effect in trials with high or unclear risks of bias.

Two review authors (AG and JL) will independently assess bias for each study and for each relevant outcome. When there is disagreement regarding bias, the authors will discuss and conclude with assistance from a third review author (MK). When there is an unclear or high risk of bias for a particular outcome within an individual study, we will conduct sensitivity analyses by removing that study from the meta-analysis.

Measures of treatment effect

Primary outcomes

We will calculate the risk ratio (RR) and corresponding 95% confidence intervals (CI) for gain of 2 or more lines of BCVA in the study eye (dichotomous variable) from baseline to 12 months following surgery (or study enrollment). Ideally, BCVA in participants randomized to receive the IMT in a predetermined study eye will be compared with BCVA in the predetermined study eye of participants who did not receive the IMT implant in either eye. However, if these types of study designs are not available, we will consider within-person designs that compared BCVA between eyes that received the implant and fellow eyes that did not received the implant in the same participant. We will calculate RRs as per the criteria set out in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011).

We will assess QoL by calculating the mean difference and corresponding 95% CIs in the change from baseline to 12 months in participants randomized to receive the IMT and in participants who did not receive the implant as outlined in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011). If within-person studies are included, in which the eye with the IMT is compared with the fellow eye within the same participant, we will not be able to compare QoL outcomes between treatments; however, we will describe changes in QoL from baseline. In order to account for the variety of QoL scales (e.g. Activity of Daily Living Scale Questionnaire and the National Eye Institute Visual Functioning Questionnaire), we will use the standardized mean difference to compute summary statistics for QoL when included studies used different QoL measurement scales.

Secondary outcomes
  1. Gain of 2 or more lines of BCVA.

  2. Change in QoL.

  3. Mean change in BCVA.

  4. Loss of 2 or more lines of BCVA.

We will calculate the RR and corresponding 95% CIs for gain of 2 or more lines of BCVA from baseline to six months and 18 months following surgery (or study enrollment). We will assess QoL by calculating the mean difference and corresponding 95% CIs in the change from baseline to six months and 18 months following surgery (or study enrollment).

We also will calculate the mean difference and 95% CIs for the change in BCVA (continuous variable, expressed as logMAR) from baseline (time of surgery) to six, 12, and 18 months of follow-up. If BCVA is not expressed as logMAR, we will attempt to calculate it from provided data. For continuous variables, we will calculate the mean difference as outlined in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011).

Additionally, we will calculate the RR and corresponding 95% CI for loss of 2 or more lines of BCVA from baseline to six, 12, and 18 months following surgery (or study enrollment).

We will perform statistical analyses using The Cochrane Collaboration's Review Manager 5 software (RevMan 2012).

Adverse effects and surgical complications

Since the IMT is implanted monocularly, adverse effects and surgical complications can only occur in the eye receiving the intervention. For adverse effects and surgical complications (see Secondary outcomes), we will provide a narrative summary that reports the proportion of eyes experiencing these events.

Additional outcomes of importance to participants

For additional outcomes of importance to participants, we also will provide a narrative summary that reports the proportion of participants experiencing these outcomes (see Secondary outcomes).

Unit of analysis issues

If RCTs are available that assess differences between participants who receive the implant and participants who do not receive the implant, the unit of analysis will be the individual. Ideally, such trials should report the criteria used to determine which eye was to receive the IMT implant as well as which eye was to serve as the study eye in the control group, that is, the eye with the best or worse visual acuity at baseline, or determined randomly when both eyes had equal baseline visual acuity. However, if only randomized within-person designs are available, the unit of analysis for the primary intervention (BCVA) will be the eye. We will document whether studies using within-person designs accounted for intra-person correlations.

Dealing with missing data

Whenever possible, we will contact study authors for missing data that were not available in published reports. We will give the authors four weeks to reply to our requests, after which time we will proceed with information available from searching. We will not attempt any imputation for missing data. When data are missing for visual acuity outcomes, we will examine the reasons for missing data, the amount of missing data, and the comparability of missing data among treatment groups. We will conduct analyses with only the available data, and then qualitatively assess the potential impact of the missing data. Whenever data are not sufficiently available for quantitative analysis (e.g. missing measures of variability, number of participants at risk), we will not conduct the meta-analysis but will describe results in a narrative form.

Assessment of heterogeneity

We will assess clinical and methodologic heterogeneity among studies qualitatively by examining differences in participant characteristics, differences in follow-up periods, and differences in how outcomes were measured. We will assess statistical heterogeneity among trial results using a Chi2 test, as well as by consideration of the direct of effect of individual studies and visual inspection of overlap in the 95% CIs in forest plots generated in Review Manager 5. We will use the I2 statistic to assess statistical inconsistency across studies. An I2 value greater than 50% will be indicative of substantial statistical heterogeneity.

Assessment of reporting biases

We will present a funnel plot for each outcome when 10 or more studies are included in a meta-analysis. We will plot effect estimates on the horizontal axis and the standard error of each trial on the vertical axis. We will judge funnel plot asymmetry by visual inspection. We will try to judge whether asymmetry is due to publication bias or due to the tendency of smaller studies to produce different effect sizes for various reasons as outlined in Chapter 10 of the Cochrane Handbook for Systematic Reviews of Interventions (Sterne 2011). We will present a full description of funnel plot interpretation with the cautionary note that such interpretation will be subjective and probably speculative.

Data synthesis

When there is great variation among studies with respect to baseline characteristics, how the intervention was provided, assessment of outcomes, or follow-up periods, we will not conduct a meta-analysis, but will provide a qualitative summary. Whenever there is no evidence of clinical, methodologic, or statistical heterogeneity (I2 = 50% or less), we will use a fixed-effect model when fewer than three studies are included in a meta-analysis and a random-effects model when three or more studies are included, as described in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011). In order to account for the variety of QoL scales (Activity of Daily Living Scale Questionnaire and the National Eye Institute Visual Functioning Questionnaire), we will use the standardized mean difference to compute summary statistics for QoL.

Subgroup analysis and investigation of heterogeneity

When we find substantial heterogeneity, we will explore heterogeneity by investigating differences in implant model, participant characteristics (i.e. age, baseline vision, type of macular lesion), and length of follow-up. If no apparent reason can be identified and the cause of heterogeneity cannot be explained, we will not conduct meta-analyses.

Sensitivity analysis

We have described previously sensitivity analyses for using data extracted from figures and for handling missing participant outcome data. When applicable, we will conduct additional sensitivity analyses to determine the impact of changes in inclusion criteria such as:

  • exclusion of within-person studies that did not appropriately account for intra-person correlation;

  • exclusion of lower quality methodologic studies (i.e. studies with high or unclear risk of bias for any domains for primary outcomes);

  • exclusion of unpublished data; and

  • exclusion of industry-funded studies.

If the only data available are unpublished or industry-funded, we will not perform sensitivity analyses.

Acknowledgements

We would like to thank the Cochrane Eyes and Vision Group for their assistance in preparing the protocol and developing the search strategies. We thank Barbara Hawkins and other peer reviewers for comments on the protocol.

Richard Wormald (Co-ordinating Editor for CEVG) acknowledges financial support for his CEVG research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS or the Department of Health.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Retinal Degeneration] explode all trees
#2 MeSH descriptor: [Macular Degeneration] explode all trees
#3 MeSH descriptor: [Retinal Neovascularization] explode all trees
#4 MeSH descriptor: [Choroidal Neovascularization] explode all trees
#5 MeSH descriptor: [Macula Lutea] explode all trees
#6 ((macul* or retina* or choroid*) near/4 degener*)
#7 ((macul* or retina* or choroid*) near/4 neovasc*)
#8 maculopath*
#9 (macul* near/2 lutea*)
#10 (macul* near/3 dystroph*)
#11 (macul* near/2 syndrome)
#12 ((macul* or geographic) near/2 atroph*)
#13 ((macul* or retina*) near/2 edema*)
#14 (AMD or ARMD or CNV)
#15 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14
#16 MeSH descriptor: [Prostheses and Implants] explode all trees
#17 MeSH descriptor: [Prosthesis Implantation] explode all trees
#18 MeSH descriptor: [Miniaturization] explode all trees
#19 MeSH descriptor: [Telescopes] explode all trees
#20 IMT*
#21 Prosthe*
#22 Telescop*
#23 microtelescop*
#24 #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23
#25 #15 and #24

Appendix 2. MEDLINE (OvidSP) search strategy

1. Randomized Controlled Trial.pt.
2. Controlled Clinical Trial.pt.
3. (randomized or randomised).ab,ti.
4. placebo.ab,ti.
5. drug therapy.fs.
6. randomly.ab,ti.
7. trial.ab,ti.
8. groups.ab,ti.
9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
10. exp animals/ not humans.sh.
11. 9 not 10
12. exp Macular Degeneration/
13. exp Retinal Degeneration/
14. exp Retinal Neovascularization/
15. exp Choroidal Neovascularization/
16. exp Macula Lutea/
17. ((macul* or retina* or choroid*) adj4 degener*).tw.
18. ((macul* or retina* or choroid*) adj4 neovasc*).tw.
19. Maculopath*.tw.
20. (macul* adj2 lutea*).tw.
21. (macul* adj3 dystroph*).tw.
22. (macul* adj2 syndrome).tw.
23. ((macul* or geographic) adj2 atroph*).tw.
24. ((macul* or retina*) adj2 edema*).tw.
25. (AMD or ARMD or CNV).tw.
26. or/13-24
27. exp "Prostheses and Implants"/
28. exp Prosthesis Implantation/
29. exp Miniaturization/
30. exp Telescopes/
31. IMT*.tw.
32. Prosthe*.tw.
33. Telescop*.tw.
34. microtelescop*.tw.
35. or/27-34
36. 11 and 26 and 35

Appendix 3. EMBASE.com search strategy

#1 'randomized controlled trial'/exp
#2 'randomization'/exp
#3 'double blind procedure'/exp
#4 'single blind procedure'/exp
#5 random*:ab,ti
#6 #1 OR #2 OR #3 OR #4 OR #5
#7 'animal'/exp OR 'animal experiment'/exp
#8 'human'/exp
#9 #7 AND #8
#10 #7 NOT #9
#11 #6 NOT #10
#12 'clinical trial'/exp
#13 (clin* NEAR/3 trial*):ab,ti
#14 ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti
#15 'placebo'/exp
#16 placebo*:ab,ti
#17 random*:ab,ti
#18 'experimental design'/exp
#19 'crossover procedure'/exp
#20 'control group'/exp
#21 'latin square design'/exp
#22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
#23 #22 NOT #10
#24 #23 NOT #11
#25 'comparative study'/exp
#26 'evaluation'/exp
#27 'prospective study'/exp
#28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti
#29 #25 OR #26 OR #27 OR #28
#30 #29 NOT #10
#31 #30 NOT (#11 OR #23)
#32 #11 OR #24 OR #31
#33 'retina maculopathy'/exp
#34 'retina degeneration'/exp
#35 'retina macula degeneration'/exp
#36 'retina neovascularization'/exp
#37 'subretinal neovascularization'/exp
#38 'retina macula lutea'/exp
#39 ((macul* OR retina* OR choroid*) NEAR/4 degener*):ab,ti
#40 ((macul* OR retina* OR choroid*) NEAR/4 neovasc*):ab,ti
#41 maculopath*:ab,ti
#42 (macul* NEAR/2 lutea*):ab,ti
#43 (macul* NEAR/3 dystroph*):ab,ti
#44 (macul* NEAR/2 syndrome):ab,ti
#45 ((macul* OR geographic) NEAR/2 atroph*):ab,ti
#46 ((macul* OR retina*) NEAR/2 edema*):ab,ti
#47 amd:ab,ti OR armd:ab,ti OR cnv:ab,ti
#48 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47
#49 'prostheses and orthoses'/exp
#50 'implantation'/exp
#51 'telescope'/exp
#52 imt*:ab,ti
#53 prosthe*:ab,ti
#54 telescop*:ab,ti
#55 microtelescop*:ab,ti
#56 #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55
#57 #32 AND #48 AND #56

Appendix 4. PubMed search strategy

#1 ((randomized controlled trial[pt]) OR (controlled clinical trial[pt]) OR (randomised[tiab] OR randomized[tiab]) OR (placebo[tiab]) OR (drug therapy[sh]) OR (randomly[tiab]) OR (trial[tiab]) OR (groups[tiab])) NOT (animals[mh] NOT humans[mh])
#2 ((macul*[tiab] OR retina*[tiab] OR choroid*[tiab]) AND degener*[tiab]) NOT Medline[sb]
#3 ((macul*[tiab] OR retina*[tiab] OR choroid*[tiab]) AND neovasc*[tiab]) NOT Medline[sb]
#4 Maculopath*[tiab] NOT Medline[sb]
#5 (macul*[tiab] AND lutea*[tiab]) NOT Medline[sb]
#6 (macul*[tiab] AND dystroph*[tiab]) NOT Medline[sb]
#7 (macul*[tiab] AND syndrome[tiab]) NOT Medline[sb]
#8 ((macul*[tiab] OR geographic[tiab]) AND atroph*[tiab]) NOT Medline[sb]
#9 ((macul*[tiab] OR retina*[tiab]) AND edema*[tiab]) NOT Medline[sb]
#10 (AMD[tiab] OR ARMD[tiab] OR CNV[tiab]) NOT Medline[sb]
#11 #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10
#12 IMT*[tiab] NOT Medline[sb]
#13 Prosthe*[tiab] NOT Medline[sb]
#14 Telescop*[tiab] NOT Medline[sb]
#15 microtelescop*[tiab] NOT Medline[sb]
#16 #12 OR #13 OR #14 OR #15
#17 #1 AND #11 AND #16

Appendix 5. LILACS search strategy

((Macul$ OR Mácul$ OR Retina$ OR Retiniana OR Choroid$ OR Coroide) AND (Degenera$ OR Neovasculariza$) OR MH:C11.768.585$ OR MH:C11.768.585.439$ OR MH: C11.768.725$ OR MH:C23.550.589.500.725$ OR MH:C11.941.160.244$ OR MH:C23.550.589.500.145$ OR MH:A09.371.729.522$ OR maculopath$ OR AMD OR ARMD OR CNV) AND (Prosthe$ OR Prótes$ OR MH:E07.695$ OR MH:VS2.006.002.010$ OR MH:E04.650$ OR Miniaturization OR Miniaturización OR Miniaturização OR MH:J01.897.520$ OR Telescop$ OR Telescópios OR MH:E07.632.875$ OR IMT$ OR microtelescop$)

Appendix 6. AMED (OvidSP) search strategy

1. exp eye disease/
2. ((macul* or retina* or choroid*) adj4 degener*).tw.
3. ((macul* or retina* or choroid*) adj4 neovasc*).tw.
4. Maculopath*.tw.
5. (macul* adj2 lutea*).tw.
6. (macul* adj3 dystroph*).tw.
7. (macul* adj2 syndrome).tw.
8. ((macul* or geographic) adj2 atroph*).tw.
9. ((macul* or retina*) adj2 edema*).tw.
10. (AMD or ARMD or CNV).tw.
11. or/1-10
12. exp prosthesis/
13. Implants artificial/
14. IMT*.tw.
15. Prosthe*.tw.
16. Telescop*.tw.
17. microtelescop*.tw.
18. or/12-17
19. 11 and 18
20. exp eye disease/
21. ((macul* or retina* or choroid*) adj4 degener*).tw.
22. ((macul* or retina* or choroid*) adj4 neovasc*).tw.
23. Maculopath*.tw.
24. (macul* adj2 lutea*).tw.
25. (macul* adj3 dystroph*).tw.
26. (macul* adj2 syndrome).tw.
27. ((macul* or geographic) adj2 atroph*).tw.
28. ((macul* or retina*) adj2 edema*).tw.
29. (AMD or ARMD or CNV).tw.
30. or/20-29
31. exp prosthesis/
32. Implants artificial/
33. IMT*.tw.
34. Prosthe*.tw.
35. Telescop*.tw.
36. microtelescop*.tw.
37. or/31-36
38. 30 and 37

Appendix 7. CPCI-S search strategy

# 1 Topic=(((macul* OR retina* OR choroid*) NEAR/4 degener*))
# 2 Topic=(((macul* OR retina* OR choroid*) NEAR/4 neovasc*))
# 3 Topic=(maculopath*)
# 4 Topic=((macul* NEAR/2 lutea*))
# 5 Topic=((macul* NEAR/3 dystroph*))
# 6 Topic=((macul* NEAR/2 syndrome))
# 7 Topic=(((macul* OR geographic) NEAR/2 atroph*))
# 8 Topic=(((macul* OR retina*) NEAR/2 edema*))
# 9 Topic=(amd OR armd OR cnv)
# 10 #9 OR #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1
# 11 Topic=(imt*)
# 12 Topic=(prosthe*)
# 13 Topic=(telescop*)
# 14 Topic=(microtelescop*)
# 15 #14 OR #13 OR #12 OR #11
# 16 #15 AND #10

Appendix 8. OpenSIGLE search strategy

(macul* OR retina* OR choroid*) AND (degenerat* OR neovascula* OR lutea* OR dystroph* OR syndrome OR atroph* OR edema*) AND (telescop* OR implant* OR IMT* OR prosthe* OR microtelescop*)

Appendix 9. metaRegister of Controlled Trials search strategy

(macular OR retina OR choroidal) AND (telescope OR prosthetic OR IMT)

Appendix 10. ClinicalTrials.gov search strategy

(Condition) macular degeneration OR retinal degeneration OR retinal neovascularization OR choroidal neovascularization OR macula lutea OR Maculopathy OR macular dystrophy OR macular syndrome OR macula edema OR retinal edema OR AMD OR ARMD OR CNV

(Intervention) telescope OR telescopes OR microtelescope OR prostheses OR prosthesis OR prosthetic OR IMT

Appendix 11. ICTRP search strategy

macular degeneration OR retinal degeneration OR retinal neovascularization OR choroidal neovascularization OR macula lutea OR Maculopathy OR macular dystrophy OR macular syndrome OR macula edema OR retinal edema OR AMD OR ARMD OR CNV = Condition AND telescope OR telescopes OR microtelescope OR prostheses OR prosthesis OR prosthetic OR IMT = Intervention

Appendix 12. FDA search strategy

combinations of the following key words: "implantable miniature telescope, "IMT," retina AND implant," "Vision Care Ophthalmic Technologies," "macular degeneration," and "AMD"

Contributions of authors

Amisha Gupta and Jessica Lam wrote the protocol.
Peter Custis, Stephen Munz, Donald Fong, and Marguerite Koster provided substantial and critical comments to the protocol.

All authors approved the final version of the protocol.

Declarations of interest

The authors have no conflicts of interest.

Sources of support

Internal sources

  • Kaiser Permanente, USA.

External sources

  • Methodologic support provided by the Cochrane Eyes and Vision Group US Project funded by Grant 1 U01 EY020522-01, National Eye Institute, National Institutes of Health, USA.

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