We read with interest the study by Özsaygili et al. in which the authors report that the presence or absence of posterior vitreous detachment (PVD) purportedly had no influence on the efficacy of aflibercept intravitreal injections in patients with diabetic macular oedema (DMO). We question the validity of this conclusion since it is known that eyes with attached vitreous require more injections to manage exudative age-related macular degeneration than eyes with PVD.1 This is presumed to be due to interference with macular access by anti-vascular endothelial growth factor (anti-VEGF) by the posterior vitreous cortex. The same mechanism of action could be expected in eyes with DMO. Thus, there may be alternative explanations for the observed lack of an effect of PVD status on the response to aflibercept. We hypothesize that the findings are due to both the unreliable diagnosis of PVD by spectral domain optical coherence tomography (SD-OCT) alone, and the possible presence of vitreoschisis.
Previous studies have shown that SD-OCT is not a robust way to diagnose PVD, since the positive predictive value is only approximately 50%.2, 3 Rather, ultrasound is the recommended way to detect complete PVD (Figure 1).2 Did Özsaygili et al. perform ultrasound in their patients? If not, they would be unable to determine true PVD status, and the validity of their conclusion needs to be called into question.
Additionally, it is unclear from the study by Özsaygili et al. wheth...
We read with interest the study by Özsaygili et al. in which the authors report that the presence or absence of posterior vitreous detachment (PVD) purportedly had no influence on the efficacy of aflibercept intravitreal injections in patients with diabetic macular oedema (DMO). We question the validity of this conclusion since it is known that eyes with attached vitreous require more injections to manage exudative age-related macular degeneration than eyes with PVD.1 This is presumed to be due to interference with macular access by anti-vascular endothelial growth factor (anti-VEGF) by the posterior vitreous cortex. The same mechanism of action could be expected in eyes with DMO. Thus, there may be alternative explanations for the observed lack of an effect of PVD status on the response to aflibercept. We hypothesize that the findings are due to both the unreliable diagnosis of PVD by spectral domain optical coherence tomography (SD-OCT) alone, and the possible presence of vitreoschisis.
Previous studies have shown that SD-OCT is not a robust way to diagnose PVD, since the positive predictive value is only approximately 50%.2, 3 Rather, ultrasound is the recommended way to detect complete PVD (Figure 1).2 Did Özsaygili et al. perform ultrasound in their patients? If not, they would be unable to determine true PVD status, and the validity of their conclusion needs to be called into question.
Additionally, it is unclear from the study by Özsaygili et al. whether vitreoschisis, defined as a split within the posterior vitreous cortex (Figure 2), was observed or documented. Although SD-OCT has the ability to detect vitreoschisis4–6, “what we see depends mainly on what we look for”, as Sir John William Lubbock once wrote. If there were cases in the series assembled by Özsaygili et al. with anomalous PVD and vitreoschisis, this could be incorrectly diagnosed as PVD, and the access of aflibercept into the macula may have been hindered by the outer wall of the vitreoschisis cavity (Figure 2), giving another reason for the false impression that PVD plays no role on aflibercept response in patients with diabetic macular oedema.
In conclusion, we agree with Sir Lubbock that we see what we seek and thus invite the authors to re-examine their data with the foregoing in mind.
References:
1. Sebag J. Vitreous in age-related macular degeneration therapy - The medium is the message. Retina. 2015;35(9):1715-1718. doi:10.1097/IAE.0000000000000718.
2. Hwang ES, Kraker JA, Griffin KJ, Sebag J, Weinberg D V, Kim JE. Accuracy of Spectral-Domain OCT of the Macula for Detection of Complete Posterior Vitreous Detachment. Ophthalmol Retin. 2020;4(2):148-153. doi:10.1016/j.oret.2019.10.013.
3. Abraham JR, Ehlers JP. Posterior Vitreous Detachment: Methods for Detection. Ophthalmol Retin. 2020;4(2):119-121. doi:10.1016/j.oret.2019.12.014.
4. Sebag J. Vitreoschisis. Graefe’s Arch Clin Exp Ophthalmol. 2008;246(3):329-332. doi:10.1007/s00417-007-0743-x.
5. Gupta P, Yee KMP, Garcia P, et al. Vitreoschisis in macular diseases. Br J Ophthalmol. 2011;95(3):376-380. doi:10.1136/bjo.2009.175109.
6. Sebag J. Vitreoschisis in diabetic macular edema. Invest Ophthalmol Vis Sci. 2011;52(11):8455-8456. doi:10.1167/iovs.11-8333.
To the Editor:
We appreciate the comments by Wei Gui and J. Sebag about Ozsaygili Cemal’s article titled ‘The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema.’1 In our study, we used the video display mode to obtain more reliable results while evaluating the posterior vitreous detachment (PVD) status with spectral-domain optical coherence tomography (SD-OCT). In a recent clinical study comparing the PVD status with ocular ultrasonography (US) and SD-OCT in patients with diabetic macular oedema (DMO), it was reported that video display mode SD-OCT showed total agreement (100% in video display mode) with US.2 We used the video display mode in all patients instead of a single cross-sectional view and excluded patients with poor image quality. Since it was a retrospective study, we could not have the chance to perform US, but excluding these patients from the study in patients where any of the 2 independent retina specialists (CO, BK) disagreed on the PVD status draws attention as factors that increase the validity of our data. In addition, the International Vitreomacular Traction Study Group, including doctor J. Sebag, has classified the posterior vitreous-macular relationship based on OCT and has mostly replaced USG with OCT in our current clinical practice.3
All eyes in our study were examined for vitreoschisis and similar anomalous PVD using SD-OCT video display mode. As you mentioned, SD-OCT has the abili...
To the Editor:
We appreciate the comments by Wei Gui and J. Sebag about Ozsaygili Cemal’s article titled ‘The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema.’1 In our study, we used the video display mode to obtain more reliable results while evaluating the posterior vitreous detachment (PVD) status with spectral-domain optical coherence tomography (SD-OCT). In a recent clinical study comparing the PVD status with ocular ultrasonography (US) and SD-OCT in patients with diabetic macular oedema (DMO), it was reported that video display mode SD-OCT showed total agreement (100% in video display mode) with US.2 We used the video display mode in all patients instead of a single cross-sectional view and excluded patients with poor image quality. Since it was a retrospective study, we could not have the chance to perform US, but excluding these patients from the study in patients where any of the 2 independent retina specialists (CO, BK) disagreed on the PVD status draws attention as factors that increase the validity of our data. In addition, the International Vitreomacular Traction Study Group, including doctor J. Sebag, has classified the posterior vitreous-macular relationship based on OCT and has mostly replaced USG with OCT in our current clinical practice.3
All eyes in our study were examined for vitreoschisis and similar anomalous PVD using SD-OCT video display mode. As you mentioned, SD-OCT has the ability to detect vitreoschisis.4,5 However, we had the chance to observe that the SD-OCT video display mode can make the fine distinction between vitreoschisis and artefact more reliably than single-section images and thanks to J. Sebag's letter for the opportunity to emphasize this once again. We think that the SD-OCT video imaging mode should be kept in mind by clinicians as it provides dynamic evaluation like USG and increases the reliability of static cross-sectional images which can rarely lead to erroneous interpretations.
We have applied the same number of injections to all eyes in our study and evaluated the short-term treatment response. However, as we mentioned in our study, further studies with longer follow-up are needed regarding the effects of PVD status on injection requirement. After intravitreal injection, larger molecules may be more exposed to the molecular sieve effect of Balaz’s in the posterior vitreous cortex6, but aflibercept also may be too small to be affected by the molecular sieve effect. Not only the presence of the attached posterior vitreous cortex but also vitreous glycation and different amounts of vitreous that had glycated cross-links and hyaluronan can also affect the permeability coefficient for diffusion7 and treatment response. The answer to whether the effect of the posterior vitreous on the treatment response is more than a mechanical barrier will be elucidated by future studies. We thank Dr. Wei Gui and J. Sebag for the interest in our study and we welcome further comments, questions, and suggestions.
Cemal OZSAYGILI, Bekir KUCUK, Yener YILDIRIM
None of the authors has any financial/conflicting interests to disclose.
References
1. Özsaygili C, Küçük B, Yildirim Y. The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema [published online ahead of print, 2020 Jul 29]. Br J Ophthalmol. 2020;bjophthalmol-2020-316155. doi:10.1136/bjophthalmol-2020-316155
2. Pessoa B, Coelho J, Malheiro L, et al. Comparison of Ocular Ultrasound Versus SD-OCT for Imaging of the Posterior Vitreous Status in Patients With DME. Ophthalmic Surg Lasers Imaging Retina. 2020;51(4):S50-S53. doi:10.3928/23258160-20200401-07
3. Duker, J. S., Kaiser, P. K., Binder, S., de Smet, M. D., Gaudric, A., Reichel, E., Sadda, S. R., Sebag, J., Spaide, R. F., & Stalmans, P. (2013). The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology, 120(12), 2611–2619. https://doi.org/10.1016/j.ophtha.2013.07.042
4. Gupta, P., Yee, K. M., Garcia, P., Rosen, R. B., Parikh, J., Hageman, G. S., Sadun, A. A., & Sebag, J. (2011). Vitreoschisis in macular diseases. The British journal of ophthalmology, 95(3), 376–380. https://doi.org/10.1136/bjo.2009.175109
5. Sebag J. Vitreoschisis in diabetic macular edema. Invest Ophthalmol Vis Sci. 2011;52(11):8455-8456. doi:10.1167/iovs.11-8333.
6. Balazs EA. Die Mikrostruktur und Chemie des Glaskörpers [Microstructure and chemistry of the vitreous body]. Ber Zusammenkunft Dtsch Ophthalmol Ges. 1968;68:536-572.
7. Lee O-T, Good SD, Lamy R, et al. Advanced glycation end product accumulation reduces vitreous permeability. Invest Ophthalmol Vis Sci 2015;56:2892–2897.
We were intrigued by the study by Yang et al[1] recently published in the British Journal of Ophthalmology. They conducted a detailed analysis of the fundus screening results of 5606 infants over 5 years in tertiary neonatal intensive care units (NICUs) in four medical centres in Shanghai, China. They found the detection rate of retinopathy of prematurity (ROP)to be 15.9%, and the detection rate of type 1 ROP (1.1%) was lower than that previously reported. The mean gestational age (GA) and birth weight (BW) of infants with ROP have also decreased. Therefore, they suggest modifying the criteria of Chinese ROP screening to GA <32 weeks or BW <1600 g. Application of these criteria to the studied cohort yielded a 98.4% sensitivity, with the infants requiring fundus screening reduced by 43.2%. Therefore, these criteria would reduce medical costs significantly. This is of great significance to the screening and treatment of ROP in China, which has a huge population and regional medical resource imbalances.
However, the study also had issues that need further discussion. First, the patient cohort was not a continuous population-based cohort, and the authors did not clearly state the specific criteria for screening. Therefore, the rate could be the detection rate rather than the true incidence. In addition, the development and general conditions of these patients from NICUs are significantly different from those of the general population. Therefore, although it was a r...
We were intrigued by the study by Yang et al[1] recently published in the British Journal of Ophthalmology. They conducted a detailed analysis of the fundus screening results of 5606 infants over 5 years in tertiary neonatal intensive care units (NICUs) in four medical centres in Shanghai, China. They found the detection rate of retinopathy of prematurity (ROP)to be 15.9%, and the detection rate of type 1 ROP (1.1%) was lower than that previously reported. The mean gestational age (GA) and birth weight (BW) of infants with ROP have also decreased. Therefore, they suggest modifying the criteria of Chinese ROP screening to GA <32 weeks or BW <1600 g. Application of these criteria to the studied cohort yielded a 98.4% sensitivity, with the infants requiring fundus screening reduced by 43.2%. Therefore, these criteria would reduce medical costs significantly. This is of great significance to the screening and treatment of ROP in China, which has a huge population and regional medical resource imbalances.
However, the study also had issues that need further discussion. First, the patient cohort was not a continuous population-based cohort, and the authors did not clearly state the specific criteria for screening. Therefore, the rate could be the detection rate rather than the true incidence. In addition, the development and general conditions of these patients from NICUs are significantly different from those of the general population. Therefore, although it was a relatively representative multi-centre study, these results may not fully represent the incidence in the whole region. More population-based studies on ROP screening in a wider area could supplement and enrich the data of this study, which would provide a more comprehensive and clearer assessment of the incidence of ROP in Shanghai and China.
Second, this was a retrospective study. The authors mentioned that the results could be used as a reliable basis to improve the ROP screening guideline in China, which is insufficiently rigorous. Recent reports show that more mature infants and those with a higher BW are also at risk of developing severe ROP in developing countries [2, 3]. Dou et al [4] reported 20 cases of stage 5 ROP in north-western China, among whom 2 had GA >34 weeks and 4 had BW >2000 g. A prospective study in two medical centres in Shanghai found that if their criteria (GA ≤33 weeks or BW ≤1750 g) were adopted, any infant with ROP who needed treatment would be identified, and the number of infants needing examinations could be reduced by 16.9%[5]. If further prospective observations were conducted to examine the criteria recommended in this study (GA <32 weeks or BW <1600 g) and take the current guideline as a control, it would be more convincing.
Finally, many paediatric patients are referred to Shanghai from neighbouring areas. The investigators did not specify whether the infants were first screened in their medical centres or other hospitals. Therefore, the selection bias of the study could not be evaluated, which weakened the credibility of the results. If the authors could further explain the source and regional distribution of the participants, the results would be more convincing.
Liang Wang, Zifeng Zhang, Manhong Li, Yusheng Wang
Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
Correspondence to Zifeng Zhang, Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China; Email: zzffmmu@163.com; Yusheng Wang, Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China; Email: wangys003@126.com
Funding Grants from the National Natural Science Foundation of China (81770936)
References
1 Yang Q, Zhou X, Ni Y, et al. Optimised retinopathy of prematurity screening guideline in China based on a 5-year cohort study. Br J Ophthalmol, doi: 1136/bjophthalmol-2020-316401
2 Zhang Z, Li M, Wang Y, et al. Analysis of retinopathy of prematurity with birth weight higher than 2 kg in Xi'an area. Chin J Ophthalmol 2014;50:184-8.
3 Chen Y, Li X. Characteristics of severe retinopathy of prematurity patients in China: a repeat of the first epidemic? Br J Ophthalmol 2006;90:268-71.
4 Dou G, Li M, Zhang Z, et al. Demographic profile and ocular characteristics of stage 5 retinopathy of prematurity at a referral center in Northwest China: implications for implementation. BMC Ophthalmol 2018;18. doi: 10.1186/s12886-018-0975-z
5 Xu Y, Zhou X, Zhang Q, et al. Screening for retinopathy of prematurity in China: a neonatal units-based prospective study. Invest Ophthalmol Vis Sci 2013;54:8229-36
In their review and meta-analysis, Hedengran and coworkers1 report no relative therapeutic benefit of preservative-free (PF) therapies over benzalkonium chloride (BAK)-preserved ones. Should the costlier PF medications therefore be abandoned, or should we question this conclusion?
Ten of the 16 comparative trials analysed were of short duration, (between 15 and 90 days), the longest taking 6 months. Once-a-day medication was used in each trial, yet the dose response curve for BAK toxicity shows that each additional drop of BAK-containing medication doubles the likelihood of lissamine green corneal staining2 and increases the risk of early failure of glaucoma surgery.3 BAK toxicity is slow in onset increasing over time, due to its continual accumulation within ocular tissues.3 Thus, inconsistencies between experimental studies, which document the harmful effects of BAK and clinical trials, which do not, likely relate to the timing, dosing and duration of glaucoma therapy.4 Two to 12 week trials comparing BAK with alternatively preserved eyedrops, or PF formulations have shown no convincing differences in ocular tolerability, yet the benefits from switching from once-a-day preserved to PF therapy, accrue several months later.4 Longer term transition to alternatively preserved, or PF formulations improves tolerability, and there is good evidence that substituting PF tafluprost for BAK-containing latanoprost significantly improves tolerability.3 So sh...
In their review and meta-analysis, Hedengran and coworkers1 report no relative therapeutic benefit of preservative-free (PF) therapies over benzalkonium chloride (BAK)-preserved ones. Should the costlier PF medications therefore be abandoned, or should we question this conclusion?
Ten of the 16 comparative trials analysed were of short duration, (between 15 and 90 days), the longest taking 6 months. Once-a-day medication was used in each trial, yet the dose response curve for BAK toxicity shows that each additional drop of BAK-containing medication doubles the likelihood of lissamine green corneal staining2 and increases the risk of early failure of glaucoma surgery.3 BAK toxicity is slow in onset increasing over time, due to its continual accumulation within ocular tissues.3 Thus, inconsistencies between experimental studies, which document the harmful effects of BAK and clinical trials, which do not, likely relate to the timing, dosing and duration of glaucoma therapy.4 Two to 12 week trials comparing BAK with alternatively preserved eyedrops, or PF formulations have shown no convincing differences in ocular tolerability, yet the benefits from switching from once-a-day preserved to PF therapy, accrue several months later.4 Longer term transition to alternatively preserved, or PF formulations improves tolerability, and there is good evidence that substituting PF tafluprost for BAK-containing latanoprost significantly improves tolerability.3 So short duration studies are unlikely to reveal substantive differences.4
Several methodological issues within this systematic review merit consideration. First, there is no protocol registration, which questions its transparency. Such protocols safeguard against biased post hoc decisions in review methods, such as selective outcome reporting. Second, there is no flow diagram presenting the process of report selection. Third, cross-over trials were considered as parallel in this meta-analysis, leading to a unit-of-analysis error, which should be avoided. Appropriate unbiased methodology does exist to impute within-patient differences to incorporate cross-over trials into a meta-analysis.5 Fourth, there was no risk-of-bias assessment across studies, such as a funnel plot and an asymmetry test, to elicit evidence of publication bias. A risk-of-bias in individual studies’ evaluation was performed utilizing an old Cochrane tool. Recently, a revised Cochrane risk-of-bias tool (the RoB 2.0) for randomized trials has been introduced, and is now the preferred option.6 Last but not least every meta-analysis should include the GRADE approach for grading the strength and quality of evidence.
Unfortunately, this review and most published literature focus on mild glaucoma therapy-related ocular surface disease (GTR-OSD). The dosing and number of IOP-lowering medications needed for glaucoma control increase with disease duration so studies to determine the optimal formulations needed to avert longer term moderate/severe GTR-OSD are sorely needed.3 We agree with the authors’ statement that the “study lengths are short, especially in the context of BAK-preserved eyedrop use often being lifelong”, but are unable to accept the conclusion that BAK-containing and PF medications do not differ with respect to tolerability and therapy outcome.
Anastasios G. Konstas1, Gábor Holló2, Andreas Katsanos3, Konstadinos G. Boboridis1, Anna-Bettina Haidich4, Gordon N. Dutton5.
1: 1st and 3rd University Departments of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece;
2: Tutkimusz Ltd and Eye Center, Prima Medica Health Centers, Budapest, Hungary;
3: Ophthalmology Department, University of Ioannina, Ioannina, Greece;
4: Department of Hygiene, Social-Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece;
5: Department of Ophthalmology, Caledonian University, Glasgow, UK.
Correspondence to: Anastasios G. Konstas, 1st and 3rd University Departments of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece; email: agkonstas@gmail.com
References
1. Hedengran A, Steensberg AT, Virgili G, Azuara-Blanco A, Kolko M. Efficacy and safety evaluation of benzalkonium chloride preserved eye-drops compared with alternatively preserved and preservative-free eye-drops in the treatment of glaucoma: a systematic review and meta-analysis. Br J Ophthalmol 2020;104:1512-18.
2. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma 2008;17:350–5.
3. Konstas AGP, Labbe A, Katsanos A et al. The treatment of glaucoma using topical preservative-free agents: an evaluation of safety and tolerability. Expert Opin Drug Saf 2021;20:453-66.
4. Rasmussen CA, Kaufman PL, Kiland JA. Benzalkonium chloride and glaucoma. J Ocul Pharmacol Ther 2014;30:163–9.
5. Elbourne DR, Altman DG, Higgins JP et al. Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol 2002;31:140-9.
6. Sterne JAC, Savović J, Page MJ et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898.
We read with interest this article by Ong HS et al on “Evolution of therapies for the corneal endothelium: past, present and future approaches”.
As the article mentions, Rho kinase (ROCK) inhibitors have been described in the regenerative approach to corneal endothelial injury by aiding cell proliferation.1 Due to the wide range of cellular responses controlled by the Rho kinase signalling pathway, ROCK inhibitors play a part in increasing cell adhesion and proliferation of the corneal endothelium. Their clinical use has also been reported with success in Fuch’s endothelial dystrophy and pseudophakic corneal decompensation. 0.4% Ripasudil eye drop is the common agent used in these studies.2
Enriching nutrients, antibiotics and other additives have been described in literature to add value to corneal preservation media. It would be interesting to see if addition a Rho kinase inhibitor to the donor corneal preservation medium could enhance the endothelial cell count or limit attrition over longer preservation times. The parameters of the drop in terms of strength, solubility, minimum concentration, side effects if any etc. need to be evaluated prior. Of all the methods described to improve the corneal endothelial health, this is the only one that may be extrapolated to donor corneal tissue also, for better surgical outcomes
It may be worthwhile to test if adding a ROCK inhibitor may enhance donor corneal tissue viability in storage media, under controlled...
We read with interest this article by Ong HS et al on “Evolution of therapies for the corneal endothelium: past, present and future approaches”.
As the article mentions, Rho kinase (ROCK) inhibitors have been described in the regenerative approach to corneal endothelial injury by aiding cell proliferation.1 Due to the wide range of cellular responses controlled by the Rho kinase signalling pathway, ROCK inhibitors play a part in increasing cell adhesion and proliferation of the corneal endothelium. Their clinical use has also been reported with success in Fuch’s endothelial dystrophy and pseudophakic corneal decompensation. 0.4% Ripasudil eye drop is the common agent used in these studies.2
Enriching nutrients, antibiotics and other additives have been described in literature to add value to corneal preservation media. It would be interesting to see if addition a Rho kinase inhibitor to the donor corneal preservation medium could enhance the endothelial cell count or limit attrition over longer preservation times. The parameters of the drop in terms of strength, solubility, minimum concentration, side effects if any etc. need to be evaluated prior. Of all the methods described to improve the corneal endothelial health, this is the only one that may be extrapolated to donor corneal tissue also, for better surgical outcomes
It may be worthwhile to test if adding a ROCK inhibitor may enhance donor corneal tissue viability in storage media, under controlled conditions.
REFERENCES:
1. Okumura N, Okazaki Y,Inoue R, Kazuya Kakutani, et al. Effect of the Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) on Corneal Endothelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 2016;57(3):1284-1292.
2. Moshirfar M, Parker L, Birdsong OC, et al. Use of Rho kinase Inhibitors in Ophthalmology: A Review of the Literature. Med Hypothesis Discov Innov Ophthalmol. 2018;7(3):101-111.
We read with interest the recent article by Evans et al regarding outcomes in randomised control trial of multifocal lenses in cataract surgery, and their case for development of a core outcome set.1 We wholeheartedly agree that a set of core outcomes would be hugely beneficial to multifocal intraocular lens (MIOL) studies, as there is such variation in multifocal studies currently. This has been commented on by previous Cochrane reviews2 yet there remains no consensus. Such variability makes meaningful comparison between studies difficult.
Evans’ suggests that the minimum data collected in MIOL studies should be unaided and corrected distance and near LogMAR acuity and contrast sensitivity. Also, the use of a questionnaire for patient reported outcomes that must include questions relating to spectacle independence and halos/glare.
Whilst we agree with the above measures, we feel that perhaps such a minimum data set may be insufficient particularly as it fails to address intermediate vision. We would recommend the inclusion of a defocus profile that covers distance, intermediate and near ranges. In addition, a standardised method of defocus measurement3 and analysis.4 This could be used as an adjunct to conventional visual acuity testing or indeed as a replacement. MIOLs have different add powers and light distribution profiles; consequently the choice of testing distance for near and intermediate acuity measures has a profound impact on results and hence may n...
We read with interest the recent article by Evans et al regarding outcomes in randomised control trial of multifocal lenses in cataract surgery, and their case for development of a core outcome set.1 We wholeheartedly agree that a set of core outcomes would be hugely beneficial to multifocal intraocular lens (MIOL) studies, as there is such variation in multifocal studies currently. This has been commented on by previous Cochrane reviews2 yet there remains no consensus. Such variability makes meaningful comparison between studies difficult.
Evans’ suggests that the minimum data collected in MIOL studies should be unaided and corrected distance and near LogMAR acuity and contrast sensitivity. Also, the use of a questionnaire for patient reported outcomes that must include questions relating to spectacle independence and halos/glare.
Whilst we agree with the above measures, we feel that perhaps such a minimum data set may be insufficient particularly as it fails to address intermediate vision. We would recommend the inclusion of a defocus profile that covers distance, intermediate and near ranges. In addition, a standardised method of defocus measurement3 and analysis.4 This could be used as an adjunct to conventional visual acuity testing or indeed as a replacement. MIOLs have different add powers and light distribution profiles; consequently the choice of testing distance for near and intermediate acuity measures has a profound impact on results and hence may not reflect visual function accurately. The use of a defocus curve is more robust to the variations between lenses and provides vital information for clinicians looking to assess the performance of the MIOL.
Finally, Evans suggests a post-operative interval of 6-18 months, and we entirely support the need for a long-term follow-up interval, yet feel it is beneficial to include a short-term follow-up also (<6 months) to allow for comparison and documentation of changes to measures, such as contrast sensitivity, which have been shown to improve with time5
References
1. Evans JR, de Silva SR, Ziaei M, Kirthi V, Leyland MD. Outcomes in randomised controlled trials of multifocal lenses in cataract surgery: the case for development of a core outcome set. Br J Ophthalmol. 2020;104(10):1345-1349.
2. de Silva SR, Evans JR, Kirthi V, Ziaei M, Leyland M. Multifocal versus monofocal intraocular lenses after cataract extraction. Cochrane Database Syst Rev. 2016;12:CD003169.
3. Gupta N, Wolffsohn JS, Naroo SA. Optimizing measurement of subjective amplitude of accommodation with defocus curves. J Cataract Refract Surg. 2008;34(8):1329-1338.
4. Buckhurst PJ, Wolffsohn JS, Naroo SA, et al. Multifocal intraocular lens differentiation using defocus curves. Invest Ophthalmol Vis Sci. 2012;53(7):3920-3926.
5. Law EM, Aggarwal RK, Buckhurst H, et al. Visual function and subjective perception of vision after bilateral implantation of monofocal and multifocal IOLs: a randomized controlled trial. J Cataract Refract Surg. 2020;46(7):1020-1029.
The review article by Thng ZX, De Smet MD, Lee CS, et al 1highlights the most intriguing aspects on use of immunosuppressants during and post COVID-19 pandemic. The authors have presented evidences based on various reports in a very well-structured manner and we would like to first thank and congratulate the authors for their work. The review covers the wide range of faculties of medicine where immune suppression is likely to be the main stay of treatment. At the same time, they have also very neatly presented with the “clear cut “ guidelines on the dosing of these various medications at different scenarios and patient status.
While the article additionally covers the following aspects very well ;
1) Does the use of immunosuppressive present as an independent risk factor for contracting COVID -19 in patients under them?
2) Does it affect the severity of COVID -19 ?
We have few inquiries to make to the authors regarding the use of immunosuppressive in ophthalmology during this difficult time.
The authors have used the term “high dose steroids” in their article. Firstly, we are curious to understand what would be the considered the criteria to define a “high dosage” of steroid in ophthalmology. From our understanding, it depends upon the class of steroid used and the body weight2 but should we also need to consider the duration of use and cumulative dosage over a stretch of time to define it?
The review article by Thng ZX, De Smet MD, Lee CS, et al 1highlights the most intriguing aspects on use of immunosuppressants during and post COVID-19 pandemic. The authors have presented evidences based on various reports in a very well-structured manner and we would like to first thank and congratulate the authors for their work. The review covers the wide range of faculties of medicine where immune suppression is likely to be the main stay of treatment. At the same time, they have also very neatly presented with the “clear cut “ guidelines on the dosing of these various medications at different scenarios and patient status.
While the article additionally covers the following aspects very well ;
1) Does the use of immunosuppressive present as an independent risk factor for contracting COVID -19 in patients under them?
2) Does it affect the severity of COVID -19 ?
We have few inquiries to make to the authors regarding the use of immunosuppressive in ophthalmology during this difficult time.
The authors have used the term “high dose steroids” in their article. Firstly, we are curious to understand what would be the considered the criteria to define a “high dosage” of steroid in ophthalmology. From our understanding, it depends upon the class of steroid used and the body weight2 but should we also need to consider the duration of use and cumulative dosage over a stretch of time to define it?
Also, referring to various publications , the definition also seems to vary even if the class of steroids are same but administered via a different route2,3 . Most likely it is related to the bioavailability but the term “high dose” in general, really seems to be creating a confusion to ophthalmologists. 4
Since the authors of this review are also the renowned key members of the various uveitis societies and have been involved in preparing protocols and guidelines , we like to draw their attention to revisit the issue and reach a consensus to use the term “high dose “ more judiciously by providing it with a more categorical definition.
On a final note, while the authors have advised to keep steroids/immunomodulators as low as possible, we would like to inquire on what are the recommendations for pathologies – such as retinal vasculitis, VKH ,SO , Optic neuritis ,traumatic optic neuropathy ,etc. which require “high dosage” or “mega- dosage” in a pulsed or a non-pulsed manner. 2,3,5 It would be of great value for clinicians around the world if the authors could provide their recommendations on such entities.
Reference:
1. Thng ZX, De Smet MD, Lee CS, et al COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs British Journal of Ophthalmology Published Online First: 12 June 2020. doi: 10.1136/bjophthalmol-2020-316586.
2. Sherif Z, Pleyer U: Corticosteroids in Ophthalmology: Past – Present – Future. Ophthalmologica 2002;216:305-315. doi: 10.1159/000066189.
3. Charkoudian LD, Ying GS, Pujari SS, et al. High-dose intravenous corticosteroids for ocular inflammatory diseases. Ocul Immunol Inflamm. 2012;20(2):91‐99. doi:10.3109/09273948.2011.646382.
4. Yu-Wai-Man P, Griffiths PG. Steroids for traumatic optic neuropathy. Cochrane Database Syst Rev. 2011;(1):CD006032. Published 2011 Jan 19. doi:10.1002/14651858.CD006032.pub3.
5. O’Keefe GA, Rao AN. Vogt–Koyanagi–Harada disease. Surv Ophthalmol. 2017;62(1):1–25.
I read the interesting manuscript entitled “Effect of a formulated eye drop with Leptospermum spp honey on tear film properties”. Authors have compared a formulated eye drop made of honey and regular lubricant drops finding some advantages of the honey eye drop. While the natural honey mainly composed of sugars, the beneficial effect might merely related to these simple carbohydrates. If authors have decided to find any effect, peculiarly attributed to the honey, they might design a control group with similar composition of simple carbohydrates to disclose the unclouded actual effect of the honey. On the other side, there might be some possible complications of promoting such agents as proved treatments, that have been already in use as alternative home made remedies; we have reported a case of Acanthamoeba keratitis using non-sterile honey eye drop (1).
1. Peyman A, Pourazizi M, Peyman M, Kianersi F. Natural Honey-Induced Acanthamoeba keratitis. Middle East Afr J Ophthalmol. 2020 Jan 29;26(4):243-245. doi: 10.4103/meajo.MEAJO_56_18. PMID: 32153338; PMCID: PMC7034153.
Kruglyakova, et al recently published an excellent paper about visually pertinent correlation of optic nerve hypoplasia (ONH) with intra-operative photographic measurements1. We recently reported similar findings without subjecting children to general anesthesia if ultra-widefield imaging (OPTOS; Dunfermline, UK) is available2. We agree that a MD/DD ratio greater than 3.22 (≥3.51) is consistent with clinical optic nerve hypoplasia but our direct measure of horizontal optic nerve size was even more predictive utilizing our definition of logMAR for pediatric and low vision patients3. Instead of starting from the temporal edge of the optic nerve to determine MD (macula-disk) distance, we found the center of the optic nerve more uniform. In addition, we have also noted a worrisome relationship between ONH and threshold retinopathy of prematurity4 and wonder if the authors also found any association between the two common pediatric blinding conditions ONH and ROP?
References:
1. Kruglyakova J, Garcia-Filion P, Nelson M, Borchert M. Orbital MRI versus fundus photography in the diagnosis of optic nerve hypoplasia and prediction of vision. Br J Ophthalmol. 2020;104(10):1458-1461.
2. Arnold AW, Eller AM, Smith KA, Grendahl RL, Winkle RK, Arnold RW. Direct nerve size determination and prevalent optic nerve hypoplasia in Alaska. Clin Ophthalmol. 2020;14:491—499.
3. Arnold RW. Digital values for alpha acuities. JPOS. 2020:In Press.
4. Arnold RW. Opti...
Kruglyakova, et al recently published an excellent paper about visually pertinent correlation of optic nerve hypoplasia (ONH) with intra-operative photographic measurements1. We recently reported similar findings without subjecting children to general anesthesia if ultra-widefield imaging (OPTOS; Dunfermline, UK) is available2. We agree that a MD/DD ratio greater than 3.22 (≥3.51) is consistent with clinical optic nerve hypoplasia but our direct measure of horizontal optic nerve size was even more predictive utilizing our definition of logMAR for pediatric and low vision patients3. Instead of starting from the temporal edge of the optic nerve to determine MD (macula-disk) distance, we found the center of the optic nerve more uniform. In addition, we have also noted a worrisome relationship between ONH and threshold retinopathy of prematurity4 and wonder if the authors also found any association between the two common pediatric blinding conditions ONH and ROP?
References:
1. Kruglyakova J, Garcia-Filion P, Nelson M, Borchert M. Orbital MRI versus fundus photography in the diagnosis of optic nerve hypoplasia and prediction of vision. Br J Ophthalmol. 2020;104(10):1458-1461.
2. Arnold AW, Eller AM, Smith KA, Grendahl RL, Winkle RK, Arnold RW. Direct nerve size determination and prevalent optic nerve hypoplasia in Alaska. Clin Ophthalmol. 2020;14:491—499.
3. Arnold RW. Digital values for alpha acuities. JPOS. 2020:In Press.
4. Arnold RW. Optic nerve hypoplasia potentiates retinopathy of prematurity. J Pediatr Ophthalmol Strabismus. 2008;45(4):247-249.
To the Editor,
We read with great interest the article entitled “Central corneal basal cell density and nerve parameters in ocular surface disease and limbal stem cell deficiency: a review and meta-analysis”. In the analysis, the authors found a similar reduction of basal cell density (BCD) and corneal nerve parameters between the limbal stem cell deficiency (LSCD) group and the ocular surface disorders (OSD) group. However, several missteps in the study methods occurred.
First, the analysis included ocular diseases that could lead to LSCD in the OSD group (eg, severe and chronic vernal and atopic keratoconjunctivitis, bullous keratopathy, and ocular graft-versus-host disease).[1] Second, acute microbial infectious keratitis, which is generally not considered as an OSD because of its distinct pathology, was included in the OSD group. Third, the severity of LSCD and OSD was not considered in the analysis. As previously demonstrated, the decrease in BCD and basal nerve density is positively correlated with LSCD severity.[2 3] Fourth, the overall sample size was very small. Lastly, no sensitivity/meta-regression analysis was done despite the significant heterogeneity in the OSD group.
We repeated the analysis after removing 7 studies wrongly included into the OSD group (Al-Aqaba &al, Leonardi &al, Muller &al -2 reports-, Moein &al, Cavalcanti &al, Tepelus &al) and not including them in the LSCD group because of heterogeneity of the st...
To the Editor,
We read with great interest the article entitled “Central corneal basal cell density and nerve parameters in ocular surface disease and limbal stem cell deficiency: a review and meta-analysis”. In the analysis, the authors found a similar reduction of basal cell density (BCD) and corneal nerve parameters between the limbal stem cell deficiency (LSCD) group and the ocular surface disorders (OSD) group. However, several missteps in the study methods occurred.
First, the analysis included ocular diseases that could lead to LSCD in the OSD group (eg, severe and chronic vernal and atopic keratoconjunctivitis, bullous keratopathy, and ocular graft-versus-host disease).[1] Second, acute microbial infectious keratitis, which is generally not considered as an OSD because of its distinct pathology, was included in the OSD group. Third, the severity of LSCD and OSD was not considered in the analysis. As previously demonstrated, the decrease in BCD and basal nerve density is positively correlated with LSCD severity.[2 3] Fourth, the overall sample size was very small. Lastly, no sensitivity/meta-regression analysis was done despite the significant heterogeneity in the OSD group.
We repeated the analysis after removing 7 studies wrongly included into the OSD group (Al-Aqaba &al, Leonardi &al, Muller &al -2 reports-, Moein &al, Cavalcanti &al, Tepelus &al) and not including them in the LSCD group because of heterogeneity of the study populations. We found a significant difference in the weighted mean difference of corneal nerve fiber length (P = 0.003) and a trend for a significant reduction in BCD (P = 0.06) in the LSCD group.
Because of the significant flaws in the study methods, the results of the analysis are incorrect and the conclusions are misleading. Understanding the pathophysiology and clinical characteristics of diseases is necessary to conduct a meaningful and sound meta-analysis.
We read with interest the study by Özsaygili et al. in which the authors report that the presence or absence of posterior vitreous detachment (PVD) purportedly had no influence on the efficacy of aflibercept intravitreal injections in patients with diabetic macular oedema (DMO). We question the validity of this conclusion since it is known that eyes with attached vitreous require more injections to manage exudative age-related macular degeneration than eyes with PVD.1 This is presumed to be due to interference with macular access by anti-vascular endothelial growth factor (anti-VEGF) by the posterior vitreous cortex. The same mechanism of action could be expected in eyes with DMO. Thus, there may be alternative explanations for the observed lack of an effect of PVD status on the response to aflibercept. We hypothesize that the findings are due to both the unreliable diagnosis of PVD by spectral domain optical coherence tomography (SD-OCT) alone, and the possible presence of vitreoschisis.
Previous studies have shown that SD-OCT is not a robust way to diagnose PVD, since the positive predictive value is only approximately 50%.2, 3 Rather, ultrasound is the recommended way to detect complete PVD (Figure 1).2 Did Özsaygili et al. perform ultrasound in their patients? If not, they would be unable to determine true PVD status, and the validity of their conclusion needs to be called into question.
Additionally, it is unclear from the study by Özsaygili et al. wheth...
Show MoreReply
To the Editor:
Show MoreWe appreciate the comments by Wei Gui and J. Sebag about Ozsaygili Cemal’s article titled ‘The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema.’1 In our study, we used the video display mode to obtain more reliable results while evaluating the posterior vitreous detachment (PVD) status with spectral-domain optical coherence tomography (SD-OCT). In a recent clinical study comparing the PVD status with ocular ultrasonography (US) and SD-OCT in patients with diabetic macular oedema (DMO), it was reported that video display mode SD-OCT showed total agreement (100% in video display mode) with US.2 We used the video display mode in all patients instead of a single cross-sectional view and excluded patients with poor image quality. Since it was a retrospective study, we could not have the chance to perform US, but excluding these patients from the study in patients where any of the 2 independent retina specialists (CO, BK) disagreed on the PVD status draws attention as factors that increase the validity of our data. In addition, the International Vitreomacular Traction Study Group, including doctor J. Sebag, has classified the posterior vitreous-macular relationship based on OCT and has mostly replaced USG with OCT in our current clinical practice.3
All eyes in our study were examined for vitreoschisis and similar anomalous PVD using SD-OCT video display mode. As you mentioned, SD-OCT has the abili...
We were intrigued by the study by Yang et al[1] recently published in the British Journal of Ophthalmology. They conducted a detailed analysis of the fundus screening results of 5606 infants over 5 years in tertiary neonatal intensive care units (NICUs) in four medical centres in Shanghai, China. They found the detection rate of retinopathy of prematurity (ROP)to be 15.9%, and the detection rate of type 1 ROP (1.1%) was lower than that previously reported. The mean gestational age (GA) and birth weight (BW) of infants with ROP have also decreased. Therefore, they suggest modifying the criteria of Chinese ROP screening to GA <32 weeks or BW <1600 g. Application of these criteria to the studied cohort yielded a 98.4% sensitivity, with the infants requiring fundus screening reduced by 43.2%. Therefore, these criteria would reduce medical costs significantly. This is of great significance to the screening and treatment of ROP in China, which has a huge population and regional medical resource imbalances.
Show MoreHowever, the study also had issues that need further discussion. First, the patient cohort was not a continuous population-based cohort, and the authors did not clearly state the specific criteria for screening. Therefore, the rate could be the detection rate rather than the true incidence. In addition, the development and general conditions of these patients from NICUs are significantly different from those of the general population. Therefore, although it was a r...
Dear Editor,
In their review and meta-analysis, Hedengran and coworkers1 report no relative therapeutic benefit of preservative-free (PF) therapies over benzalkonium chloride (BAK)-preserved ones. Should the costlier PF medications therefore be abandoned, or should we question this conclusion?
Show MoreTen of the 16 comparative trials analysed were of short duration, (between 15 and 90 days), the longest taking 6 months. Once-a-day medication was used in each trial, yet the dose response curve for BAK toxicity shows that each additional drop of BAK-containing medication doubles the likelihood of lissamine green corneal staining2 and increases the risk of early failure of glaucoma surgery.3 BAK toxicity is slow in onset increasing over time, due to its continual accumulation within ocular tissues.3 Thus, inconsistencies between experimental studies, which document the harmful effects of BAK and clinical trials, which do not, likely relate to the timing, dosing and duration of glaucoma therapy.4 Two to 12 week trials comparing BAK with alternatively preserved eyedrops, or PF formulations have shown no convincing differences in ocular tolerability, yet the benefits from switching from once-a-day preserved to PF therapy, accrue several months later.4 Longer term transition to alternatively preserved, or PF formulations improves tolerability, and there is good evidence that substituting PF tafluprost for BAK-containing latanoprost significantly improves tolerability.3 So sh...
We read with interest this article by Ong HS et al on “Evolution of therapies for the corneal endothelium: past, present and future approaches”.
As the article mentions, Rho kinase (ROCK) inhibitors have been described in the regenerative approach to corneal endothelial injury by aiding cell proliferation.1 Due to the wide range of cellular responses controlled by the Rho kinase signalling pathway, ROCK inhibitors play a part in increasing cell adhesion and proliferation of the corneal endothelium. Their clinical use has also been reported with success in Fuch’s endothelial dystrophy and pseudophakic corneal decompensation. 0.4% Ripasudil eye drop is the common agent used in these studies.2
Show MoreEnriching nutrients, antibiotics and other additives have been described in literature to add value to corneal preservation media. It would be interesting to see if addition a Rho kinase inhibitor to the donor corneal preservation medium could enhance the endothelial cell count or limit attrition over longer preservation times. The parameters of the drop in terms of strength, solubility, minimum concentration, side effects if any etc. need to be evaluated prior. Of all the methods described to improve the corneal endothelial health, this is the only one that may be extrapolated to donor corneal tissue also, for better surgical outcomes
It may be worthwhile to test if adding a ROCK inhibitor may enhance donor corneal tissue viability in storage media, under controlled...
We read with interest the recent article by Evans et al regarding outcomes in randomised control trial of multifocal lenses in cataract surgery, and their case for development of a core outcome set.1 We wholeheartedly agree that a set of core outcomes would be hugely beneficial to multifocal intraocular lens (MIOL) studies, as there is such variation in multifocal studies currently. This has been commented on by previous Cochrane reviews2 yet there remains no consensus. Such variability makes meaningful comparison between studies difficult.
Show MoreEvans’ suggests that the minimum data collected in MIOL studies should be unaided and corrected distance and near LogMAR acuity and contrast sensitivity. Also, the use of a questionnaire for patient reported outcomes that must include questions relating to spectacle independence and halos/glare.
Whilst we agree with the above measures, we feel that perhaps such a minimum data set may be insufficient particularly as it fails to address intermediate vision. We would recommend the inclusion of a defocus profile that covers distance, intermediate and near ranges. In addition, a standardised method of defocus measurement3 and analysis.4 This could be used as an adjunct to conventional visual acuity testing or indeed as a replacement. MIOLs have different add powers and light distribution profiles; consequently the choice of testing distance for near and intermediate acuity measures has a profound impact on results and hence may n...
The review article by Thng ZX, De Smet MD, Lee CS, et al 1highlights the most intriguing aspects on use of immunosuppressants during and post COVID-19 pandemic. The authors have presented evidences based on various reports in a very well-structured manner and we would like to first thank and congratulate the authors for their work. The review covers the wide range of faculties of medicine where immune suppression is likely to be the main stay of treatment. At the same time, they have also very neatly presented with the “clear cut “ guidelines on the dosing of these various medications at different scenarios and patient status.
While the article additionally covers the following aspects very well ;
1) Does the use of immunosuppressive present as an independent risk factor for contracting COVID -19 in patients under them?
2) Does it affect the severity of COVID -19 ?
We have few inquiries to make to the authors regarding the use of immunosuppressive in ophthalmology during this difficult time.
The authors have used the term “high dose steroids” in their article. Firstly, we are curious to understand what would be the considered the criteria to define a “high dosage” of steroid in ophthalmology. From our understanding, it depends upon the class of steroid used and the body weight2 but should we also need to consider the duration of use and cumulative dosage over a stretch of time to define it?
Also, referring to various public...
Show MoreI read the interesting manuscript entitled “Effect of a formulated eye drop with Leptospermum spp honey on tear film properties”. Authors have compared a formulated eye drop made of honey and regular lubricant drops finding some advantages of the honey eye drop. While the natural honey mainly composed of sugars, the beneficial effect might merely related to these simple carbohydrates. If authors have decided to find any effect, peculiarly attributed to the honey, they might design a control group with similar composition of simple carbohydrates to disclose the unclouded actual effect of the honey. On the other side, there might be some possible complications of promoting such agents as proved treatments, that have been already in use as alternative home made remedies; we have reported a case of Acanthamoeba keratitis using non-sterile honey eye drop (1).
1. Peyman A, Pourazizi M, Peyman M, Kianersi F. Natural Honey-Induced Acanthamoeba keratitis. Middle East Afr J Ophthalmol. 2020 Jan 29;26(4):243-245. doi: 10.4103/meajo.MEAJO_56_18. PMID: 32153338; PMCID: PMC7034153.
Kruglyakova, et al recently published an excellent paper about visually pertinent correlation of optic nerve hypoplasia (ONH) with intra-operative photographic measurements1. We recently reported similar findings without subjecting children to general anesthesia if ultra-widefield imaging (OPTOS; Dunfermline, UK) is available2. We agree that a MD/DD ratio greater than 3.22 (≥3.51) is consistent with clinical optic nerve hypoplasia but our direct measure of horizontal optic nerve size was even more predictive utilizing our definition of logMAR for pediatric and low vision patients3. Instead of starting from the temporal edge of the optic nerve to determine MD (macula-disk) distance, we found the center of the optic nerve more uniform. In addition, we have also noted a worrisome relationship between ONH and threshold retinopathy of prematurity4 and wonder if the authors also found any association between the two common pediatric blinding conditions ONH and ROP?
References:
Show More1. Kruglyakova J, Garcia-Filion P, Nelson M, Borchert M. Orbital MRI versus fundus photography in the diagnosis of optic nerve hypoplasia and prediction of vision. Br J Ophthalmol. 2020;104(10):1458-1461.
2. Arnold AW, Eller AM, Smith KA, Grendahl RL, Winkle RK, Arnold RW. Direct nerve size determination and prevalent optic nerve hypoplasia in Alaska. Clin Ophthalmol. 2020;14:491—499.
3. Arnold RW. Digital values for alpha acuities. JPOS. 2020:In Press.
4. Arnold RW. Opti...
To the Editor,
Show MoreWe read with great interest the article entitled “Central corneal basal cell density and nerve parameters in ocular surface disease and limbal stem cell deficiency: a review and meta-analysis”. In the analysis, the authors found a similar reduction of basal cell density (BCD) and corneal nerve parameters between the limbal stem cell deficiency (LSCD) group and the ocular surface disorders (OSD) group. However, several missteps in the study methods occurred.
First, the analysis included ocular diseases that could lead to LSCD in the OSD group (eg, severe and chronic vernal and atopic keratoconjunctivitis, bullous keratopathy, and ocular graft-versus-host disease).[1] Second, acute microbial infectious keratitis, which is generally not considered as an OSD because of its distinct pathology, was included in the OSD group. Third, the severity of LSCD and OSD was not considered in the analysis. As previously demonstrated, the decrease in BCD and basal nerve density is positively correlated with LSCD severity.[2 3] Fourth, the overall sample size was very small. Lastly, no sensitivity/meta-regression analysis was done despite the significant heterogeneity in the OSD group.
We repeated the analysis after removing 7 studies wrongly included into the OSD group (Al-Aqaba &al, Leonardi &al, Muller &al -2 reports-, Moein &al, Cavalcanti &al, Tepelus &al) and not including them in the LSCD group because of heterogeneity of the st...
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