Dear Editor,

We read the article published by Fieß, et al (1) with considerable interest and laud them on their study and the large cohort. Considerable work has been done earlier, which looks at factors associated with refractive errors, however few studies document association with birth weight. Keeping this in mind, we feel that there are a few points requiring further clarity in this article.

The authors mention their inability to control for factors such as paternal refractive error and family history. However, previous studies not only discuss the paternal refractive error and family history, but also expand the affecting factors to include the number of myopic parents. (2) In the study design described by Höhn et al. where comprehensive information on living conditions and birth weight was collected via computer-assisted telephone interviews, (3) information on number of myopic parents could also have been collected, and would have proven to be an important covariate in the analysis.

The authors also report that 8369 participants provided birth weight data, of which 45 were excluded due to unreliable self-reported data [<1000g (n=7) or >6000g (n=38)]. However, tables 2 and 3 report analysed results based on 8369 participants not 8324 (after exclusion of the 45). Even though 45 is an insignificant number, and does not affect the results as such, this aspect of the results needs further clarity.

Lastly, while the authors mention, further factors that affect BCVA and refractive errors such as amount of outdoor activity, near work in childhood and adolescence, prematurity (4,5) and gestational age, the non-inclusion of these possible confounders in their analysis makes it difficult to plan public health interventions based on these results. In the present form, the results of association of birth weight with myopic refractive error are significant but emphasise the need for further studies which control for gestational age, prematurity and other factors mentioned above, while studying the association, so that the effect can be isolated to birth weight. Public health interventions can then be planned accordingly.

We appreciate the opportunity to be able to discuss our views on the subject and the article in question.

References

1. Fieß A, Schuster AK, Nickels S, et al, Association of low birth weight with myopic refractive error and lower visual acuity in adulthood: results from the population-based Gutenberg Health Study (GHS), British Journal of Ophthalmology 2019;103:99-105.
2. Jones LA, Sinnott LT, Mutti DO, Mitchell GL, Moeschberger ML, Zadnik K. Parental history of myopia, sports and outdoor activities, and future myopia. Invest Ophthalmol Vis Sci. 2007;48(8):3524-32.
3. Höhn R, Kottler U, Peto T, et al. The ophthalmic branch of the Gutenberg Health Study: study design, cohort profile and self-reported diseases. PLoS One. 2015;10(3):e0120476. Published 2015 Mar 16. doi:10.1371/journal.pone.0120476
4. Cook A, White S, Batterbury M, et al. Ocular growth and refractive error development in premature infants without retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2003;44:953–960.
5. Fieß A, Kölb-Keerl R, Knuf M, et al. Axial Length and Anterior Segment Alterations in Former Preterm Infants and Full-Term Neonates Analyzed With Scheimpflug Imaging. Cornea 2017;36:821–7. 


Dear Editor,
We have read with great interest the article by Singhal et al 1 on 'Clinical presentation and management of corneal fistula'. The authors have rightly highlighted the point that failure to perform simple test like Seidel test in cases of corneal ulcer, can lead to missing the diagnosis of corneal fistula, which in turn can lead to serious complications like endophthalmitis, panophthalmitis and phthisis bulbi.
One of the complications of persistent corneal fistula is the formation of anterior capsular cataract. It would have been more insightful if the authors had mentioned as to how many patients had developed anterior capsular cataract during follow up, as this can lead to a change in the future management of the eye.
Also, the authors have not mentioned the type of anaesthesia for doing the procedure. As creating the grooves around perforation to tuck in the tenons graft is difficult due to the friability of corneal tissue, the type of anaesthesia has a bearing on the intra operative surgical procedure. As doing the technique in topical anaesthesia will be technically challenging and administration of peribulbar block could lead to extrusion of the intraocular contents or extension of the perforation.
Although the study mentions the surgical technique for closing the fistula with a tenons patch graft, it does not mention the regimen of postoperative medical management.
In the discussion, the authors have mentioned that the cyanoacrylate glue application can lead to iritis. But all the cases included in the study had fistula size of not more than 3 mm. There is enough evidence to state that perforations and fistulas of sizes 2-3 mm can be closed safely with cyanoacrylate glue without any migration of the glue into the anterior chamber and obviate the need for other surgical treatment.2,3
References :
1. Singhal D, Sahay P, Maharana PK, et al. Clinical presentation and management of corneal fistula. Br J Ophthalmol. 2019 ;103:530-533.
2. Jhanji V, Young AL, Mehta JS, et al. Management of corneal perforation. Surv Ophthalmol. 2011 ;56:522-38.
3. Korah S, Selvin SS, Pradhan ZS, et al. Tenons Patch Graft in the Management of Large Corneal Perforations. Cornea 2016;35:696–9

In their report, entitled “Intravitreal chemotherapy in retinoblastoma: expanded use beyond intravitreal seeds“, Abramson and corkers report on the successful use of intravitreal chemotherapy in 52 patients for subretinal seeds and recurrent retinal tumours [1]. They state that, prior to their experience, intravitreal chemotherapy had been used exclusively to control persistent or recurrent vitreous seeding in retinoblastoma that had been refractory to systemic intravenous or intra-arterial chemotherapy.

In fact, intravitreal chemotherapy as an adjuvant treatment for both subretinal seeds and recurrent retinal tumours, including its use instead of systemic chemotherapy in the setting of chemothermotherapy for small unresponsive primary retinoblastomas, has been in regular use already for a decade at the Ocular Oncology Service, Helsinki University Eye Hospital. Indeed, three of the first four patients that we reported during the congress of the International Society of Ocular Oncology in 2009 [2], and published in 2011 [3], received intravitreal methotrexate for reasons other than vitreous seeds. Subsequent experience with intravitreal chemotherapy with methotrexate and, later, with melphalan has strengthened our initial findings, as does the comprehensive report of Abramson and coworkers.

1. Abramson DH, Ji X, Francis JH, et al. Intravitreal chemotherapy in retinoblastoma: expanded use beyond intravitreal seeds. Br J Ophthalmol 2018 Jun 6. pii: bjophthalmol-2018-312037. doi: 10.1136/bjophthalmol-2018-312037.

2. Kivelä T, Eskelin S, Lindahl P, Majander A. Intravitreal methotrexate monotherapy as salvage treatment for recurrent retinoblastoma after standard chemoreduction. In: ISOO Metting 2009: Programme and Abstracts, p. 279. http://www.xcdsystem.com//isoo/webimages/pdf%20%236%20isoo%202009%20camb... (accessed on November 1, 2018)

3. Kivelä T, Eskelin S, Paloheimo M. Intravitreal methotrexate for retinoblastoma. Ophthalmology 2011;118(8):1689, 1689.e1-6. doi: 10.1016/j.ophtha.2011.02.005.

To the Editor,
Intravitreal antivascular endothelial growth factor (VEGF) agents undeniably have many clinical applications and we read with great interest the recent meta-analysis published in your journal by Low et al1 comparing the effectiveness and harms of these agents in three retinal disorders.
We would first like to thank the authors for their exhaustive review and synthesis of the evidence in this area. The conclusions they reached served to confirm what many of us had already suspected.2 Nevertheless, the article features some important methodological flaws and inadequate reporting of data that we would like to highlight to ensure that readers are in a position to interpret the findings of the meta-analysis correctly.
In relation to reporting issues, we were surprised to see that Table 1, which is quite creative and unique in terms of systematic review tables, does not include a list of the studies analyzed for each section. The authors, for example, state that they included two clinical trials comparing aflibercept and ranibizumab, but they do not specify which ones. This detracts from the transparency of the study and makes it difficult to review the findings. We also noticed a lack of uniformity within the figures, as some of the studies are listed by author name and others by author name and year of publication. In addition, Figure 3 shows data from the 2011 study by Biswas P, Sengupta S, Choudhary R, et al for the 18-24–month but not the 12-month period, and there is no explanation for this omission in the text.
We also detected some methodological issues that depart from international recommendations.3,4 On replicating the meta-analysis using the data provided by Low et al1 in the STATA statistical package, we did not find the same results as those reported. In Figure 2, the mean difference (95% CI) given for months in the GEFAL study is 2.36 (-0.72 to 5.44), whereas we obtained a difference of 1.90 (95 CI%: -0.73 to 4.53). This modifies the magnitude of the overall measure (in our case, -0.25; 95% CI: -1.39 to 0.89), but not its direction or interpretation. We observed a similar finding for the 18-24 month period for the CATT study, as Figure 2B shows a difference of -1.00 (95% CI: -3.54 to 1.54), whereas we observed an overall difference of -0.51 (9 5CI% :-1.91 to 0.88).
Another aspect that caught our attention is that some of the meta-analysis subgroup analyses were underpowered (<50%), but this is not mentioned in the results or discussed as an important limitation. The authors also make no mention of publication bias, which is normally evaluated using a funnel plot or Egger’s plot, as per reporting guidelines.3,4 Finally, Low et al1 reported that they analyzed the quality of the individual studies included in their systematic review and show the corresponding results in Table 1. However, they did not report on any sensitivity analyses to identify lower-quality studies that should have possibly been excluded or studies that might have significantly affected results.
The authors clearly attempted to cover many aspects in their systematic review, from the effectiveness and harms to the cost and cost-effectiveness of three VGEF agents in three conditions: neovascular age-related macular degeneration, diabetic macular oedema (DME), and branch retinal vein occlusion. It is not our place to comment on the wisdom or not of analyzing so many aspects, but we would like to point out that just one study was analyzed to assess the evidence on the cost-effectiveness of bevacizumab versus aflibercept versus ranibizumab in DME. Despite the commendable efforts of the authors, they failed to report on some key methodological aspects from the PRISMA (Preferred Reported Items for Systematic Review and Meta-Analyses) checklist3 and the Cochrane Handbook for Systematic Reviews of Interventions.4
REFERENCES
1. Low A, Faridi A, Bhavsar KV, Cockerham GC, Freeman M, Fu R, et al. Comparative effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis. Br J Ophthalmol. 8 de noviembre de 2018;
2. Cai S, Bressler NM. Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T. Curr Opin Ophthalmol. noviembre de 2017;28(6):636-43.
3. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 21 de julio de 2009;339:b2535.
4. Higgins JP, Green, Sally. Cochrane Handbook for Systematic Reviews of Interventions [Internet]. The Cochrane Collaboration. Disponible en: https://handbook-5-1.cochrane.org/