Mauschitz et al. (1) conducted a meta-analysis to investigate the association of systemic medications with age-related macular degeneration (AMD) in the general population. A pooled odds ratios (95% confidence intervals [CIs]) of lipid-lowering drugs (LLD) and antidiabetic drugs for any AMD were 0.85 (0.79 to 0.91) and 0.78 (0.66 to 0.91), respectively. In contrast, late AMD was not significantly associated with systemic medications. There is an information that antidiabetics, lipid-lowering agents, and antioxidants could theoretically be repurposed for AMD treatment (2). I present information regarding the effect of antidiabetic medications on the risk of AMD.

Blitzer et al. (3) conducted a case-control study and metformin use was significantly associated with reduced odds of AMD, presenting dose dependent manner. But metformin did not have an effect of protecting diabetic retinopathy. In contrast, Gokhale et al. (4) conducted a retrospective cohort study to evaluate the effect of metformin on the risk reduction of AMD. The adjusted hazard ratio (95% CI) of patients prescribed metformin (with or without other antidiabetic medications) against those prescribed any other antidiabetic medication only for AMD was 1.02 (0.92 to 1.12). Vergroesen et al. (5) conducted a cohort study and a lower risk of AMD was not observed in patients with metformin, but other diabetes medication was significantly associated with a lower risk of AMD.

Anyway, clinical trials are needed to specify the inconsistent relationship between antidiabetic medications and the risk reduction of AMD.

References
1. Mauschitz MM, Verzijden T, Schuster AK, et al. Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans. Br J Ophthalmol 2022 doi: 10.1136/bjo-2022-321985
2. Nadeem U, Xie B, Xie EF, et al. Using advanced bioinformatics tools to identify novel therapeutic candidates for age-related macular degeneration. Transl Vis Sci Technol 2022;11(8):10.
3. Blitzer AL, Ham SA, Colby KA, Skondra D. Association of metformin use with age-related macular degeneration: A case-control study. JAMA Ophthalmol 2021;139(3):302-309.
4. Gokhale KM, Adderley NJ, Subramanian A, et al. Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study. Br J Ophthalmol 2022 doi: 10.1136/bjophthalmol-2021-319641
5. Vergroesen JE, Thee EF, Ahmadizar F, et al. Association of diabetes medication with open-angle glaucoma, age-related macular degeneration, and cataract in the Rotterdam Study. JAMA Ophthalmol 2022;140(7):674-681.

It is generally believed that retinal neurons stop growing in number after birth in humans.1, 2 But recent research has shown retinal neurogenesis in neonatal 1-3 month old monkeys.3 This poses the question of how the sclera and the retina grow during emmetropization. The ora serrata is reported to be 2 mm wide growing to 6-7mm (approximately 5mm difference) in adult life as the scleral tunic grows more than the retina.4 The vitreous chamber depth in newborns is 10.6mm long and also grows roughly by 6 mm to an adult axial value of 17mm on average.5 It is then possible that during the first 3 months of human life, at that rapid growth phase from 17mm to 19mm in mean axial length,6 the retina could grow at least 1mm to compensate in part for that rapid elongation. The eyes of males and females have only a 0.1mm difference at birth with very small differences in body length and head circumference, but bigger born babies have longer eyes with less powerful corneas,7 so a bigger born girl may have a bigger eye with flatter cornea than a smaller born male. When adulthood is reached, women have eyes shorter than those of men by 0.7mm, with steeper corneas and more powerful crystalline lenses.8 As the cornea stabilizes by ages 2-3 in infants, these differential growth patterns are probably established early in life.4 And as usually happens not only among males and females, emmetropic or low hyperopic eyes that develop low corneal powers are longer than eyes that stay with steep corneas (first described by Sorsby9). It is believed that this coordination between ocular components is produced by defocus mechanisms that affect the retino-scleral message that governs ocular growth.10
It has been shown that the limit after which a long axial length ends in myopic maculopathy is shorter in women vs. men.11 One of the believed reasons for myopic maculopathy, besides hypoxia, is retinal thinning as the non-growing retina adapts to an increased rate of myopic scleral elongation during school years. The case is that when environmental triggers (like lagging when reading black text in low illuminated environments) begin to act after age 6 and myopia develops, some of those developing myopic eyes have normal corneas of 43.00D and medium axial lengths of 23mm for 6 year old children, but others have 46.00D corneas with 22mm long eyes, and even some have 40.00D corneas with 24mm long eyes. These ones will grow 1mm in the next 10 years if remaining emmetropic, but about 2-3mm if developing myopia. Following what is suggested about ocular growth, these eyeballs with low powered corneas (or lenses) may be longer eyes which are at higher risk of reaching the threshold for myopic maculopathy.
It is possible that not only the axial length and gender should be monitored with ocular growth curves,12 but the unique data of the keratometry could be split by tertiles in ocular growth curves of boys and girls (as keratometry will not change with growth during school years). This relationship between fundus myopic changes in children and keratometry has been also shown in the recent paper by Gong et al. which has motivated our short report.13 Those children with flatter corneas could be devoted to special care as they are the ones who possibly rank high in axial length dimensions and may be the ones more prone to myopic maculopathy.14

1. Young RW. Cell proliferation during postnatal development of the retina in the mouse. Brain Res 1985;353(2):229-39.
2. Kubota R, Hokoc JN, Moshiri A, et al. A comparative study of neurogenesis in the retinal ciliary marginal zone of homeothermic vertebrates. Brain Res Dev Brain Res 2002;134(1-2):31-41.
3. Tkatchenko AV, Walsh PA, Tkatchenko TV, et al. Form deprivation modulates retinal neurogenesis in primate experimental myopia. Proc Natl Acad Sci U S A 2006;103(12):4681-6.
4. Iribarren R. Crystalline lens and refractive development. Prog Retin Eye Res 2015;47:86-106.
5. Rozema JJ, Herscovici Z, Snir M, Axer-Siegel R. Analysing the ocular biometry of new-born infants. Ophthalmic Physiol Opt 2017.
6. Mutti DO, Mitchell GL, Jones LA, et al. Axial growth and changes in lenticular and corneal power during emmetropization in infants. Invest Ophthalmol Vis Sci 2005;46(9):3074-80.
7. Blomdahl S. Ultrasonic measurements of the eye in the newborn infant. Acta Ophthalmol (Copenh) 1979;57(6):1048-56.
8. Iribarren R, Morgan IG, Hashemi H, et al. Lens power in a population-based cross-sectional sample of adults aged 40 to 64 years in the Shahroud Eye Study. Invest Ophthalmol Vis Sci 2014;55(2):1031-9.
9. Benjamin B, Davey JB, Sheridan M, et al. Emmetropia and its aberrations; a study in the correlation of the optical components of the eye. Spec Rep Ser Med Res Counc (G B) 1957;11(293):1-69.
10. Wallman J, Winawer J. Homeostasis of eye growth and the question of myopia. Neuron 2004;43(4):447-68.
11. Hashimoto S, Yasuda M, Fujiwara K, et al. Association between Axial Length and Myopic Maculopathy: The Hisayama Study. Ophthalmol Retina 2019;3(10):867-73.
12. Tideman JWL, Polling JR, Vingerling JR, et al. Axial length growth and the risk of developing myopia in European children. Acta Ophthalmol 2018;96(3):301-9.
13. Gong W, Cheng T, Wang J, et al. Role of corneal radius of curvature in early identification of fundus tessellation in children with low myopia. Br J Ophthalmol 2022.
14. Galan MM TW, Iribarren R. El rol de la longitud axial y la queratometría en el seguimiento de niños miopes Oftalmologia Clinica y Experimental 2021;14(2).

Dear Editor.

We read with interest the manuscript published by Sakamoto et al, on behalf of the Japanese Retina and Vitreous Society, titled: Increased incidence of endophthalmitis after vitrectomy relative to face mask-wearing during COVID-19 pandemic”.[1] In this manuscript, the authors discuss their results after comparing the total prevalence of infectious endophthalmitis among patients that underwent ocular surgery, before and after the peak of the SARS-CoV-2 pandemic in Japan.[1] The authors should be commended due to the level of complexity and significant effort needed to coordinate several centers simultaneously, as well as the detailed description provided in the manuscript regarding the clinical presentation, microbiological results, and outcomes of all cases. Interestingly and despite the low rate of positive vitreous cultures, the authors were able to isolate oral bacteria among several of the cases that developed endophthalmitis during the pandemic, including one caused by Staphylococcus lugdunensis; a pathogen typically hard to eliminate with mechanical washing bacteria, because it accumulates behind the auricle.[1] With all this evidence, the authors provided a compelling argument regarding the inappropriate wearing of face masks could increase the risk of postoperative endophthalmitis. Nevertheless, we believe that there are a few important considerations that the authors may need to address before making such an assumption.
As a start, we can mention a few methodological irregularities that are hallmarks of any retrospective study and thus unavoidable. However, some may carry a significant relevance to the outcome such as the lack of rigor in the definition of postoperative endophthalmitis in the inclusion/exclusion criteria. In their manuscript, Sakamoto et al considered postoperative endophthalmitis, any intraocular infection that developed within 42 days after surgery. Although we agree with this definition, we must clarify that this definition refers to the maximum time elapsed between the invasion of the intraocular space by the offending bacteria, which is during surgery, and the development of the first clinical symptoms. Which, depending on the bacteria's virulence, could be up to 6 weeks. The latest optical coherence tomography and ultrasound biomicroscopy evidence have shown that sclerotomies after a pars plana vitrectomy seal between 8 and 15 days after surgery, even after a sutureless approach.[2 3] Therefore, it is highly unlikely that the source of infection originated after this time, as the authors seem to imply. Moreover, although the authors’ argument that face masking may increase the contamination of the periocular area makes sense, laboratory evidence has shown that there is no difference between bacterial dispersion toward the ocular surface when comparing different types of masks and masking techniques (tape in the superior border of the mask and no tape).[4] Nevertheless, we do agree that wearing a face mask before or during surgery may induce ocular surface changes such as dry eye disease and subclinical infectious keratitis, which might hypothetically increase the risk of endophthalmitis. If we consider the possible exhaustion of the surgical team (human error), scarcity of surgical disinfectants, and other factors that occurred during the peak of the SARS-CoV-2 pandemic, this should place the source of the infection during surgery and not after it. The high prevalence of Streptococcal endophthalmitis in the SARS-CoV-2 mask period (as defined by the authors), supports indeed the notion that contamination may come from the oral flora, very similar to the reports of post intravitreal injection endophthalmitis. However, bacteria such as Streptococcus mitis and Streptococcus salivarius are usually described as low-virulence or opportunistic pathogens. Therefore, the onset time of the clinical symptoms of endophthalmitis, information not described in the manuscript, could have helped the reader to infer if the contamination occurred during surgery or during the postoperative time.
Finally, the result observed regarding the prevalence of postoperative endophthalmitis in the only-phacoemulsification group, is not consistent with the main hypothesis suggested by the authors, and points in the opposite direction. If how the patient uses the mask during the postoperative period is indeed a determinant factor in endophthalmitis development and, considering that the prevalence of endophthalmitis after vitrectomy is usually lower in comparison to other surgical procedures [5]; we should have expected a proportional increase in the prevalence in all three groups. The latter might be the result of a lack of a sample calculation and therefore an error type 1, which should have been mentioned in the limitation section. A throughout analysis of the surgical circumstance per group is also lacking. Consequently, it is not clear at this time if other significant risk factors (trauma, intraocular foreign body, posterior capsule rupture) for endophthalmitis were present or not during surgery. A multivariate analysis, controlling for several other risk factors should be enough to shed light on this matter.
We congratulate Sakamoto et al for this outstanding contribution. We will look forward to their reply.

References:
1. Sakamoto T, Terasaki H, Yamashita T, et al. Increased incidence of endophthalmitis after vitrectomy relative to face mask wearing during COVID-19 pandemic. Br J Ophthalmol 2022 doi: 10.1136/bjophthalmol-2022-321357[published Online First: Epub Date]|.
2. Keshavamurthy R, Venkatesh P, Garg S. Ultrasound biomicroscopy findings of 25 G Transconjuctival Sutureless (TSV) and conventional (20G) pars plana sclerotomy in the same patient. BMC Ophthalmol 2006;6:7 doi: 10.1186/1471-2415-6-7[published Online First: Epub Date]|.
3. Sawada T, Kakinoki M, Sawada O, Kawamura H, Ohji M. Closure of sclerotomies after 25- and 23-gauge transconjunctival sutureless pars plana vitrectomy evaluated by optical coherence tomography. Ophthalmic Res 2011;45(3):122-8 doi: 10.1159/000318875[published Online First: Epub Date]|.
4. Angaramo S, Law JC, Maris AS, et al. Potential impact of oral flora dispersal on patients wearing face masks when undergoing ophthalmologic procedures. BMJ Open Ophthalmol 2021;6(1):e000804 doi: 10.1136/bmjophth-2021-000804[published Online First: Epub Date]|.
5. AlBloushi B, Mura M, Khandekar R, et al. Endophthalmitis Post Pars Plana Vitrectomy Surgery: Incidence, Organisms' Profile, and Management Outcome in a Tertiary Eye Hospital in Saudi Arabia. Middle East Afr J Ophthalmol 2021;28(1):1-5 doi: 10.4103/meajo.MEAJO_424_20[published Online First: Epub Date]|.

We read with interest the article by Sarker et al(1) in which they compared the outcomes of trabeculectomy versus Ahmed glaucoma valve (AGV) implantation in Sturge–Weber syndrome (SWS) patients with secondary glaucoma aged 11-62 years. As it noted in the paper, the authors found that complete success rates after 24 months were 80% and 70% in the AGV and trabeculectomy groups, respectively, and qualified success rates were 90% and 85% at same period in the AGV and trabeculectomy groups, respectively. We were delighted to get the conclusion that both AGV implant and trabeculectomy appeared to be safe and efficacious in controlling glaucoma secondary to SWS.
As it reported by Mohamed et al., the complete success rate and qualified success rate (intraocular pressure≤17mmHg) of trabeculectomy reported were 80% and 100% at 12 postoperative follow-up month, respectively(2). However, the qualified success rate (90%) of AGV implantation in SWS patients with secondary glaucoma is higher than that reported by Hamush et al. (79%)(3) and Kaushik et al. (76%)(4) at 2 years of follow-up. Meanwhile, the trabeculectomy with MMC success rate in this study was comparable to other studies about primary glaucoma(5, 6), but the success rate of tube shunt surgery was higher than in prior reports. The qualified success rate of Baerveldt implantation for patients who not had undergone previous incisional ocular surgery was 73% in Primary Tube Versus Trabeculectomy (PTVT) study(6) and 75% reported by Islamaj et al(5)at 2 years of follow-up. The qualified success rates of AGV implantation and Baerveldt implantation for patients with refractory glaucoma were 76% and 68% at 2 years of follow-up, respectively(7).
This more favorable result of AGV implantation relative to previous reports may because this small sample size study excluded 8 patients (16.7%), enrolled patients may uncomplete 2 years of review, or most of them are older than 18 years old compared with other study about SWS patients with secondary glaucoma(3, 4). The study enrolled eyes may at lower risk of surgical failure than that excluded from the study. As the authors mentioned, a total of 48 patients in glaucoma associated with SWS were surgically treated and 8 patients were excluded because of unreliable follow-ups and/or incomplete case records. Substantial differences in the success rate of cases with and without follow-up may overestimate the success rates of two surgeries and prove misleading on interpreting the results in this small sample size, retrospective study. What’s more, mean±SD follow-up in the study was 23.15±2.36 (range, 15–24) and 22.95±2.87 (range, 13–24) in the AGV and trabeculectomy groups, respectively, which may indicate incomplete 2 years of review for some patients. Patients who experienced successful surgical treatment at 15 months may subsequently experience treatment failure at 24 months. It’s better to supplement the number of patients at each follow up visit.
In conclusion, since the small sample size, it is better to supplement the outcomes of eight patients excluded from the study and the number of patients at each follow up visit so as to yield more convincing results.

Reference

1. Sarker BK, Malek MA, Mannaf SMA, Iftekhar QS, Mahatma M, Sarkar MK, et al. Outcome of trabeculectomy versus Ahmed glaucoma valve implantation in the surgical management of glaucoma in patients with Sturge-Weber syndrome. Br J Ophthalmol. 2021;105(11):1561-5.
2. Mohamed T, Salman A, Elshinawy R. Trabeculectomy with Ologen implant versus mitomycin C in congenital glaucoma secondary to Sturge Weber Syndrome. International journal of ophthalmology. 2018;11(2):251-5.
3. Hamush N, Coleman A, Wilson M. Ahmed glaucoma valve implant for management of glaucoma in Sturge-Weber syndrome. American journal of ophthalmology. 1999;128(6):758-60.
4. Kaushik J, Parihar J, Jain V, Mathur V. Ahmed valve implantation in childhood glaucoma associated with Sturge-Weber syndrome: our experience. Eye (London, England). 2019;33(3):464-8.
5. Islamaj E, Wubbels R, de Waard P. Primary baerveldt versus trabeculectomy study after 5 years of follow-up. Acta ophthalmologica. 2020;98(4):400-7.
6. Gedde SJ, Feuer WJ, Lim KS, Barton K, Goyal S, Ahmed IIK, et al. Treatment Outcomes in the Primary Tube Versus Trabeculectomy Study after 3 Years of Follow-up. Ophthalmology. 2020;127(3):333-45.
7. Christakis P, Zhang D, Budenz D, Barton K, Tsai J, Ahmed I. Five-Year Pooled Data Analysis of the Ahmed Baerveldt Comparison Study and the Ahmed Versus Baerveldt Study. American journal of ophthalmology. 2017;176:118-26.