Visual prognosis and complications of congenital ectopia lentis: study protocol for a hospital-based cohort in Zhongshan Ophthalmic Center

Introduction Congenital ectopia lentis (CEL) is a rare ocular disease characterised by the dislocation or displacement of the lens. Patients with mild lens dislocations can be treated with conservative methods (eg, corrective eyeglasses or contact lenses). In contrast, patients with severe CEL usually require surgical management. However, few studies have focused on the visual prognosis and complications in conservative and surgical management of patients. This study aims to investigate the prognosis and complications in patients with CEL with conservative and surgical management, which is vital for CEL management, especially the choice of surgical timing and surgical method. Methods and analysis A cohort study will be conducted at Zhongshan Ophthalmic Center. We plan to recruit 604 participants diagnosed with CEL and aged ≥3 years old. Patients with mild lens subluxation and stable visual conditions will be included in the non-surgical group and follow-up at 1, 2 and 3 years after enrolment. Patients with severe lens subluxation who accept CEL surgery will be included in the surgical group. Different surgical techniques, including phacoemulsification, in-the-bag intraocular lens implantation (with or without capsular tension ring) and trans-scleral fixation, will be used depending on the severity of dislocation. Patients will be followed up at 3 months, and 1, 2 and 3 years postoperatively. Over a 5-year follow-up period, patients will receive a detailed ocular examination, including optometry, biological measurement, specular microscopy, ultrasound biomicroscopy, anterior segment and posterior segment optical coherence tomography (OCT), OCT angiography, echocardiography and questionnaires on vision-related quality of life. The primary outcome is the change of best-corrected visual acuity and the incidence of complications in both groups. Ethics and dissemination Ethics approval was obtained from the ethics committee of the Zhongshan Ophthalmic Center (number: 2022KYPJ207). Study findings will be published in a peer-reviewed journal. Trial registration number NCT05654025.

Line 33 -what does "follow-up cohort" refer to? Later, this is called a follow-up prospective study. The authors should clarify their terminology and maintain consistency in the manuscript (it is called "follow-up cohort," "prospective follow-up cohort," "prospective clinical trial," "longitudinal cohort study")these should all be standardized Line 43is the surgery dictated by surgeon preference or study protocol? It may be useful to at least name the different surgical techniques in the abstract Line 50 -"endokeratoscope" should be changed to "specular microscopy" (an endokeratoscope is the instrument used to perform the diagnostic, not the diagnostic itself) Page 8 Line 13authors may consider mentioning CEL with no known systemic manifestations Line 22add reference to support this statement Line 26authors should mention that this is LogMAR acuity Line 47again, what is a prospective, follow-up cohort? Isn't this redundant?
Page 11 Line 13specify that this is LogMAR acuity Line 14 -how is "progressive subluxation" defined and how will this be objectively monitored in a standardized and auditable fashion? Line 24the authors should specify plans for patients with fluoroquinolone allergy Page 12 Line 5do the authors plan to use iris hooks or capsular retraction hooks? Line 30givne that the authors specify the exact medications in the preoperative routine, the same should be done for postoperative Page 13 Line 11how will the state of the zonules be objectively assessed?
Page 14 Examinationsit would be very helpful if the examinations are described in the same order as they are listed in the secondary outcomes section Page 15 Line 21more details are needed on how UBM will be used to assess the zonules Figure 1 -instead of "assessed for surgical indications," the authors should list the criteria for surgery and then the branching will follow that if yes, the patient has surgery and if no, they are followed with observation  what study activities will occur at each study time point. I also have several small suggestions for changes to strengthen the manuscript outlined line by line below: Response：Thank you for your professional comments. Our previous research found that children aged ≤ 3 years old only account for 8.82% of the whole CEL population (PMID: 30225232), and these children are often difficult to finish the necessary examinations. Therefore, this study only included children older than 3 years old. In this study, congenital ectopia lentis patients with different ages were included and we did not set an upper age limit for inclusion criteria considering. We have modified Figure 2 into a table format to better show the examination items to be carried out during each study period now.

Page 5
Line 22 -"treated with surgical treatment" is redundant -I would change this here (and throughout) to "surgical management" Response：Thank you for your comments. We have revised it to "surgical management" throughout the manuscript.
Line 33 -what does "follow-up cohort" refer to? Later, this is called a follow-up prospective study. The authors should clarify their terminology and maintain consistency in the manuscript (it is called "followup cohort," "prospective follow-up cohort," "prospective clinical trial," "longitudinal cohort study")these should all be standardized Response：Thank you for your comments. We have revised it to "cohort" throughout the manuscript.
Line 43is the surgery dictated by surgeon preference or study protocol? It may be useful to at least name the different surgical techniques in the abstract Response：Thank you for your comments. The surgery is dictated by the study protocol. We have revised this part in the abstract now.
Line 50 -"endokeratoscope" should be changed to "specular microscopy" (an endokeratoscope is the instrument used to perform the diagnostic, not the diagnostic itself) Response：Thank you for your comments. We have revised it accordingly.

Page 8
Line 13authors may consider mentioning CEL with no known systemic manifestations Response：Thank you for your comments. We have revised it in the "introduction" section accordingly.
Line 22add reference to support this statement Response：Thank you for your comments. We have added a reference to support this statement now.
Line 26authors should mention that this is LogMAR acuity Response：We have revised it in the "introduction" section accordingly.
Line 47again, what is a prospective, follow-up cohort? Isn't this redundant? Response：Thank you for your comments. We have revised it to "cohort" throughout the manuscript.

Page 11
Line 13specify that this is LogMAR acuity Response：Thank you for your comments. We have revised it in the manuscript. Line 14 -how is "progressive subluxation" defined and how will this be objectively monitored in a standardized and auditable fashion? Response：Thank you for your professional comments. Currently, there is indeed no recognized, objective standard for the diagnosis of "progressive subluxation"(PMID: 32155956). Considering the severity of lens dislocation in congenital ectopia lentis may increase over time, "progressive subluxation" is defined as increasing degree of zonular disruption or loosening which could be detected by ultrasound biomicroscopy (UBM) and/or slit-lamp photography after dilation.
Line 24the authors should specify plans for patients with fluoroquinolone allergy Response：Thank you for your comments. We have revised this in the manuscript. Tobramycin eye drops would be used in patients with fluoroquinolone allergy.
Page 12 Line 5do the authors plan to use iris hooks or capsular retraction hooks? Response：Thank you for your comments. We plan to stablize the bag by using iris hooks to hook onto the bag, since capsular retraction hooks are not available in our hospital. The following image is an intraoperative screenshot of us using an iris hook to stabilize the capsular bag.
Line 30givne that the authors specify the exact medications in the preoperative routine, the same should be done for postoperative. Response：Thank you for your comments. We have revised it accordingly now.
Page 13 Line 11how will the state of the zonules be objectively assessed? Response：Thank you for your comments. The state of the zonules will be objectively assessed using ultrasound biomicroscopy (UBM) and slit-lamp photography after dilation.

Page 14
Examinationsit would be very helpful if the examinations are described in the same order as they are listed in the secondary outcomes section Response：Thank you for your comments. We have reordered the examinations accordingly.
Page 15 Line 21more details are needed on how UBM will be used to assess the zonules Response：Thank you for your comments. We have added more details information on how UBM will be used to assess the zonules now. Figure 1 -instead of "assessed for surgical indications," the authors should list the criteria for surgery and then the branching will follow that if yes, the patient has surgery and if no, they are followed with observation Response：Thank you for your comments. We have revised the Figure 1 accordingly. Figure 2 this figure needs to be changed to a table or other diagram that shows exactly which diagnostics will be performed at each study visit. Response：Thank you for your suggestion. We have revised the Figure 2 into Supplemental table 1 (According to the journal's requirement: tables with more than 9 columns should be uploaded separately as a Supplemental Material file).