We have read the review article entitled “Ocular complications of cat scratch disease” Johnson A. Br J Ophthalmol 2020;0:1-7. We want to congratulate the author for this important review article, and make some contributions.
In the review article, it has been indicated that optical coherence tomography (OCT) imaging is of value to monitoring cat scratch disease (CSD), particularly for neuroretinitis and multifocal retinitis.
We would like to highlight a feature of focal retinitis with spectral domain optical coherence tomography (SD-OCT). Small areas of retinitis, less than 500 microns in diameter, can be seen on OCT imaging. These appear as areas of focal hyper-reflectivity of the inner retinal layers and decreased reflectivity causing a shadow on the outer retinal layers and choroid. This was seen in two patients presenting to our service recently with Bartonella henselae CSD diagnosed clinically and confirmed by positive serology.
The first case was a 49-year-old Caucasian male who presented with bilateral inflammatory papillitis and multifocal retinitis without a macular star, confirmed with serology as Bartonella henselae (IgG >2048). He had good presenting Snellen visual acuities of 6/5 right, 6/6 left. OCT imaging at acute presentation showed multifocal retinitis seen as small areas retinal hyper-reflectivity of the inner retina with outer retinal disruption. The disease resolved without treatment in 8 months, with...
We have read the review article entitled “Ocular complications of cat scratch disease” Johnson A. Br J Ophthalmol 2020;0:1-7. We want to congratulate the author for this important review article, and make some contributions.
In the review article, it has been indicated that optical coherence tomography (OCT) imaging is of value to monitoring cat scratch disease (CSD), particularly for neuroretinitis and multifocal retinitis.
We would like to highlight a feature of focal retinitis with spectral domain optical coherence tomography (SD-OCT). Small areas of retinitis, less than 500 microns in diameter, can be seen on OCT imaging. These appear as areas of focal hyper-reflectivity of the inner retinal layers and decreased reflectivity causing a shadow on the outer retinal layers and choroid. This was seen in two patients presenting to our service recently with Bartonella henselae CSD diagnosed clinically and confirmed by positive serology.
The first case was a 49-year-old Caucasian male who presented with bilateral inflammatory papillitis and multifocal retinitis without a macular star, confirmed with serology as Bartonella henselae (IgG >2048). He had good presenting Snellen visual acuities of 6/5 right, 6/6 left. OCT imaging at acute presentation showed multifocal retinitis seen as small areas retinal hyper-reflectivity of the inner retina with outer retinal disruption. The disease resolved without treatment in 8 months, with final Snellen visual acuities of 6/5 right and 6/6 left.
An area of retinitis was also demonstrated in a 9-year-old Caucasian girl with CSD. CSD was confirmed with positive serologic testing for Bartonella henselae (IgG >2048, IgM <20). She presented with a four-day history of reduced vision in her left eye and a gastrointestinal illness, and had recently been scratched by a stray kitten. She developed bilateral neuroretinitis with presenting Snellen visual acuities of 6/6 right and count fingers left. A small area of juxtafoveal retinitis was demonstrated on OCT in her right eye as inner retinal hyper-reflectivity, casting a shadow on the outer retina and underlying choroid. She was treated with oral doxycycline, oral rifampicin and oral prednisone. After two weeks treatment the focal retinitis was smaller but with persistent loss of inner retinal architecture and shadowing the outer retinal and choroid, and this area had reduced further after 36 days with visualization of the outer retina and choroid in the affected area.
There are few studies documenting OCT findings in CSD. Most common findings include flattening of the foveal contour, thickening of the neurosensory retina and the presence of subretinal fluid associated with neuroretinitis.[1] Exudate associated with neuroretinitis appears as multiple hyper-reflective foci in the outer plexiform layer[2] and can lead to disruption and loss of the external limiting membrane, ellipsoid zone and interdigitation zone.[3]
To our knowledge only two other paper have described the OCT finding of focal retinitis.[4,5] This OCT sign can persist for months but with gradual decreased reflectivity of the lesion and improved visualization of outer retina as the disease resolves.[4]
References
1. Ksiaa I, Abroug N, Mahmoud A, Zina S, Hedayatfar A, Attia S, Khochtali S, Khairallah M. Update on Bartonella neuroretinitis. Journal of Current Ophthalmology. 2019;31:254-61.
2. Habot-Wilner Z, Zur D, Goldstein M, Goldenberg D, Shulman S, Kesler A, Giladi M, Neudorfer M. Macular findings on optical coherence tomography in cat-scratch disease neuroretinitis. Eye. 2011;25:1064-8.
3. Mello LGM, Lima LH, Cabral T, Rodrigues MZ, Pecanha PM, Belfort R. Bartonella Quintana-associated neuroretinitis: longitudinal spectral-domain optical coherence tomographic findings. Retinal Cases & Brief Reports. 2016;0:1-6.
4. Empeslidis T, Tsauousis KT, Konidaris V, Pradeep A, Deane J. Multifocal chorioretinitis caused by Bartonella henselae: imaging findings of spectral domain optical coherence tomography during treatment with trimethoprim-sulfamethoxazole. Eye. 2014;28:907-9.
5. Pichi F, Srivastava S, Levinson A, Baynes KM, Traut C, Lowder CY. A focal chorioretinal Bartonella lesion analyzed by optical coherence tomography angiography. Ophthalmic Surg Lasers Imaging Retina. 2016;47:585-8.
Dear Editor,
We read with great interest the excellent paper by Sagiv and collegues Ocular preservation with neoadjuvant Vismodegib in patients with locally advanced periocular basal cell carcinoma.1
The article is a great contribution for a topic with a growing, but still limited worldwide experience. Our interest is to discuss the surgical approach after neoadjuvant Vismodegib.
The authors present a patient with a 5x4cm locally advanced periocular basal cell carcinoma (LAP-BCC) with small nerve perineural invasion (>0.1mm) involving lower eyelid, inner canthus and cheek. The patient showed a significant response after 10 months of Vismodegib. Anyhow, it was clearly a partial response with 3 suspicious areas of BCC after treatment. The authors decided to treat separately each area with surgery, and histology (en face sections) confirmed the presence of tumor in two. The reconstructive outcome was excellent, and at the time of publication the patient was free of disease, 11 months after surgery.
We agree with the authors, when they consider as a limitation the fact that “surgery did not always include the entire area of the original tumor”.
Most studies involving smoothened inhibitors thus far have measured clinical tumor shrinkage but not true histologic margin control. Even after a complete clinical response (CCR), there is no way to assure that it will result in a complete histological clearance (CHR).
Several authors discussed thi...
Dear Editor,
We read with great interest the excellent paper by Sagiv and collegues Ocular preservation with neoadjuvant Vismodegib in patients with locally advanced periocular basal cell carcinoma.1
The article is a great contribution for a topic with a growing, but still limited worldwide experience. Our interest is to discuss the surgical approach after neoadjuvant Vismodegib.
The authors present a patient with a 5x4cm locally advanced periocular basal cell carcinoma (LAP-BCC) with small nerve perineural invasion (>0.1mm) involving lower eyelid, inner canthus and cheek. The patient showed a significant response after 10 months of Vismodegib. Anyhow, it was clearly a partial response with 3 suspicious areas of BCC after treatment. The authors decided to treat separately each area with surgery, and histology (en face sections) confirmed the presence of tumor in two. The reconstructive outcome was excellent, and at the time of publication the patient was free of disease, 11 months after surgery.
We agree with the authors, when they consider as a limitation the fact that “surgery did not always include the entire area of the original tumor”.
Most studies involving smoothened inhibitors thus far have measured clinical tumor shrinkage but not true histologic margin control. Even after a complete clinical response (CCR), there is no way to assure that it will result in a complete histological clearance (CHR).
Several authors discussed this issue. Tang and Alcalay reported a small number of LA-BCC treated with neoadjuvant Vismodegib plus Mohs surgery (MS).2-3 Although they observed a significant tumor shrinkage, they found islands of BCC within all their debulking specimens.2-3 Ching in a series with 6 LA-BCCs,4 with bone involvement, reported that multiple superficial biopsies done after neoadjuvant Vismodegib, showed no evidence of BCC . However, all the surgically resected specimens revealed residual tumor. After this data, Ching states that the effect of Hh inhibitor is suppressive rather than curative and should be followed by definitive surgery.
Koekelkoren, after treating 4 cases with “giant” LA-BCC, indicates that resistance to
Vismodegib seems to occur more often in deep tumor planes near bone or cartilage
and suggests this may be related with suboptimal blood perfusion, resulting in lower
Vismodegib tissue levels.5
So far, we have treated 13 patients with LAP-BCC with neoadjuvant Vismodegib + MS. The first eight cases were included in a paper published last year.6 We observed 9 CCR, 3 partial responses and 1 patient progressed. Out of the 9 CCR one patient refused surgery and is without evidence of disease after 34 months. We confirmed 6/8 CHR and found persistent tumor with MS in 2 patients. With a mean follow up of 24.6 months, one patient with a CHR recurred 17 months after MS. Therefore, 3/9 cases with a CCR either had persistent tumor at the time of MS or recurred lately, probably due to skip tumor areas.
We believe this evidence supports our position. Neoadjuvant Vismodegib may lead to missing discontiguous tumor on surgery. This may eventually progress to more aggressive histology, including thin strands of BCC, immersed in dense inflammatory/scar tissue. The evaluation of surgical margins in this scenario may be challenging.
We also differ with the authors about the need of a free flap for reconstruction in this case. Due to the difference in color and texture with facial skin, we try to avoid free flaps for cheek reconstruction and prefer a Mustardé flap (or a cervicofacial flap) combined with an oculoplastic repair for the eyelids.
Bibliography
1. Sagiv O, Nagarajan P, Ferrarotto R, Kandl TJ, Thakar SD, Glisson BS, Altan M, Esmaeli B. Br J Ophthalmol. 2019 Jun;103(6):775-780. Ocular preservation with neoadjuvant vismodegib in patients with locally advanced periocular basal cell carcinoma Br J Ophthalmol. 2019 Jun;103(6):775-780
2. Tang N, Ratner D. Implementation of systemic hedgehog inhibitors in daily practice as neoadjuvant therapy. J Natl Compr Canc Netw 2017; 15:537–43
3. Alcalay J, Tauber G, Fenig E, Hodak E. Vismodegib as a neoadjuvant treatment to mohs surgery for aggressive basal cell carcinoma. J Drugs Dermatol 2015;14:219–23.
4. Ching JA, Curtis HL, Braue JA, Kudchadkar RR, Mendoza TI, Messina JL, Cruse CW, MD, Smith DJ, Harrington MA. The Impact of Neoadjuvant Hedgehog Inhibitor Therapy on the Surgical Treatment of Extensive Basal Cell Carcinoma. Ann Plast Surg 2015;74: S193–S197
5. Koekelkoren FHJ, Roodbergen SL, Baerveldt EM, Maat APWM, Monserez DA, Grunhagen DJ, Mureau MAM, de Haas ERM, PhD, Nijsten EC, Wakkee M. Vismodegib for giant, locally advanced, basal cell carcinoma and its complex position in clinical practice. JAAD Case Reports 2019; 5:267-70.
6. González AR, Etchichury D, Gil ME, Del Aguila R. Neoadjuvant Vismodegib and Mohs Micrographic Surgery for Locally Advanced Periocular Basal Cell Carcinoma. Ophthalmic Plast Reconstr Surg. 2019; 35(1):56-61.
We appreciate the authors' interest in our study. In their letter to the editor regarding our meta-analysis[1], the authors raise an issue regarding the inclusion of the diseases in the two groups i.e. limbal stem cell deficiency (LSCD) and ocular surface disease (OSD). We adhered to the categorization of the diseases as indicated or mentioned in the publications which were included in the meta-analysis. Our literature search based on combinations of various “key-words” or “key-terms” returned results as depicted in the categorization of the diseases in the study.[2,3] LSCD being a sub-set of OSD, has signs and symptoms in common with many other conditions, hence it was important that the term “limbal stem cell deficiency” appeared in the publications for the study participants to be categorized into the LSCD group.[2,3,4]
The lack of consideration of the severity of LSCD and OSD was unavoidable due to the limited data within the source publications. It is apparent that the severity of the disease may affect the corneal epithelial basal cell density (BCD) and nerve fibre parameters.[5,6] The lack of data is likely explained by the difficulty in imaging in the more severe disease when corneal transparency is reduced; the corneal basal cells and nerves are difficult to image using confocal microscopy when the cornea is not clear. This is an important factor which is highlighted in our study.[1] Furthermore, our analysis did not attempt to c...
We appreciate the authors' interest in our study. In their letter to the editor regarding our meta-analysis[1], the authors raise an issue regarding the inclusion of the diseases in the two groups i.e. limbal stem cell deficiency (LSCD) and ocular surface disease (OSD). We adhered to the categorization of the diseases as indicated or mentioned in the publications which were included in the meta-analysis. Our literature search based on combinations of various “key-words” or “key-terms” returned results as depicted in the categorization of the diseases in the study.[2,3] LSCD being a sub-set of OSD, has signs and symptoms in common with many other conditions, hence it was important that the term “limbal stem cell deficiency” appeared in the publications for the study participants to be categorized into the LSCD group.[2,3,4]
The lack of consideration of the severity of LSCD and OSD was unavoidable due to the limited data within the source publications. It is apparent that the severity of the disease may affect the corneal epithelial basal cell density (BCD) and nerve fibre parameters.[5,6] The lack of data is likely explained by the difficulty in imaging in the more severe disease when corneal transparency is reduced; the corneal basal cells and nerves are difficult to image using confocal microscopy when the cornea is not clear. This is an important factor which is highlighted in our study.[1] Furthermore, our analysis did not attempt to correlate the BCD and corneal nerve parameters in LSCD (or OSD) based on disease severity, the analysis reported the difference in these parameters in LSCD and OSD to those participants with the normal ocular surface.
The authors report the analysis of corneal nerve fibre length (CNFL) after removing 7 studies from the OSD group and suggest that CNFL was reduced in LSCD compared to OSD. However, removing these studies caused a significant increase in the overall heterogeneity as the I-square value increased to 88.7% as compared to 49.6% in the published report. Furthermore, due to the lack of data in the LSCD group (only 2 studies), it is difficult to draw meaningful conclusions. We addressed this issue of power and what conclusions could be confidently made in the limitation section of our paper. For BCD, after redoing the analysis as suggested by the authors, we did not find a significant difference in the weighted mean difference (WMD) between LSCD and OSD (P=0.11). In addition, the modified analysis showed increased heterogeneity where the I-square value increased to 61.9% compared to 56.1% in the published report. Hence, when statistically considered, we cannot conclude there exists a significant difference in BCD between OSD and LSCD, based on current evidence.
Various studies have shown reduced corneal nerve parameters and BCD even in systemic diseases like diabetes.[7] Hence, central corneal BCD and nerve fibre parameters need to be used in conjunction with both the clinical presentation and any laboratory results. After considering the Clemence et al.’s suggestions, we are confident that our analysis and method for characterizing the participants remains correct.
Meta-analysis depends on research groups spending much time and resources collecting primary data. We remain indebted to the authors of the papers we included in our analysis and again thank those that sent us missing data and responded to our queries that enabled the inclusion of their work. When more studies are completed, updated analysis and conclusions can be made on differences in BCD and corneal nerve morphology in OSD and LSCD.
Authors: Pradipta Bhattacharya, M Phil., Katie Edwards, Ph.D., Damien Harkin, Ph.D., Katrina L Schmid, PhD.
Financial Disclosures/ Conflict of Interest: None reported.
REFERENCES
1. Bhattacharya P, Edwards K, Harkin D, Schmid KL. Central corneal basal cell density and nerve parameters in ocular surface disease and limbal stem cell deficiency: a review and meta-analysis. Br J Ophthalmol 2020.
2. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009;18;151(4):W-65.
3. Shortt AJ, Tuft SJ, Daniels JT. Corneal stem cells in the eye clinic. Br Med Bull 2011;100:209–25.
4. Deng SX, Borderie V, Chan CC, Dana R, Figueiredo FC, Gomes JA, Pellegrini G, Shimmura S, Kruse FE, International Limbal Stem Cell Deficiency Working Group. Global consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency. Cornea 2019;38(3):364-75.
5. Chan EH, Chen L, Rao JY, Yu F, Deng SX. Limbal basal cell density decreases in limbal stem cell deficiency. Am J Ophthalmol 2015;160(4):678-84.
6. Deng SX, Sejpal KD, Tang Q, Aldave AJ, Lee OL, Yu F. Characterization of limbal stem cell deficiency by in vivo laser scanning confocal microscopy: a microstructural approach. Arch Ophthalmol 2012;130(4):440-5.
7. Dehghani C, Pritchard N, Edwards K, Russell AW, Malik RA, Efron N. Abnormal anterior corneal morphology in diabetes observed using in vivo laser-scanning confocal microscopy. Ocul Surface 2016;14(4):507-14.
We read the article published by Chaudhary, et al (1) with great interest and laud them on the quality and design of their study. Primary congenital blindness (PCG) poses a challenge to clinicians, both in terms of diagnosis, and treatment. (2)
We would like to bring to the authors’ notice a similar study conducted in 2017 (3) of 230 eyes of 121 PCG patients having undergone a primary CTT. This study differed from the present study in the fact that it had a longer average follow-up period of 28.87 years with a more concentrated follow-up range of 21.5-38 years. There were also two main differences in the findings of the two studies.
Contrary to the results in the present study where the infants with PCG fared better than the neonates (48.9% >6/60), the previous study found that 76.3% newborns with PCG had a vision better than 6/60. Additionally, the previous study, found visual acuity to be better than 6/60 in a greater proportion of patients (76.1%) at the last follow-up, as compared to the proportion in the study by Chaudhary et al (55.3%). Applying the WHO recommendation of measuring vision in the better eye, (4) the results improved to 89.3% in the study by Sood et al. (3)
A possible reason for these disparities between the studies could be the difference in presentation times of the patients and the study inclusion criteria. While the present study reports late presentation, over half of the patients (53%) in the earlier pub...
We read the article published by Chaudhary, et al (1) with great interest and laud them on the quality and design of their study. Primary congenital blindness (PCG) poses a challenge to clinicians, both in terms of diagnosis, and treatment. (2)
We would like to bring to the authors’ notice a similar study conducted in 2017 (3) of 230 eyes of 121 PCG patients having undergone a primary CTT. This study differed from the present study in the fact that it had a longer average follow-up period of 28.87 years with a more concentrated follow-up range of 21.5-38 years. There were also two main differences in the findings of the two studies.
Contrary to the results in the present study where the infants with PCG fared better than the neonates (48.9% >6/60), the previous study found that 76.3% newborns with PCG had a vision better than 6/60. Additionally, the previous study, found visual acuity to be better than 6/60 in a greater proportion of patients (76.1%) at the last follow-up, as compared to the proportion in the study by Chaudhary et al (55.3%). Applying the WHO recommendation of measuring vision in the better eye, (4) the results improved to 89.3% in the study by Sood et al. (3)
A possible reason for these disparities between the studies could be the difference in presentation times of the patients and the study inclusion criteria. While the present study reports late presentation, over half of the patients (53%) in the earlier publication were operated before they reached 28 days of age. Further, the present study only includes patients with enlarged corneal diameter (>12mm) and pre-surgery IOP of 22mmHg, whereas our study had 31.74% patients with corneal diameter between 10-12mm and 0.87% patients with IOP less than 20mmHg. The former constituted 42.1% of the patients with visual acuity better than 6/60, while the latter constituted 0% of the same.
The authors of the present study also conducted an in-depth analysis of causes behind poor visual outcomes, whereas the previous study focused only on three pre-determined factors, with only one in common with the present study. Needless to say, both studies add considerably to existing literature, bolstered in their endeavour by their large sample size, a rarity by itself in studies reporting long-term outcomes in PCG patients.
References:
1. Chaudhary RS, Gupta A, Sharma A, et al Long-term functional outcomes of different subtypes of primary congenital glaucoma British Journal of Ophthalmology Published Online First: 23 December 2019. doi: 10.1136/bjophthalmol-2019-315131
2. Mandal AK, Chakrabarti D. Update on congenital glaucoma. Indian J Ophthalmol 2011;59, Suppl S1:148-57
3. Sood D, Rathore A, Sood I, Singh G, Sood NN. Long-term outcome of combined trabeculotomy-trabeculectomy by a single surgeon in patients with primary congenital glaucoma. Eye (Lond). 2018;32(2):426–432. doi:10.1038/eye.2017.207
4. World Health Organization. Change the Definition of Blindness; 2020. Available at: http://www.who.int/blindness/Change%20the %20Definition%20of%20Blindness.pdf. [Accessed on 04 May 2020].
ACKNOWLEDGEMENT: The authors would like to thank Dr Shalinder Sabherwal for his review of the manuscript for this Letter in Response.
The recent study by Vega-Estrada et al highlights some of the challenges in diagnosing keratoconus in Down syndrome (DS).[1] Previous studies have shown that the cornea of individuals with DS without evidence of keratoconus appear to be steeper and thinner than the general population, both being features characteristic of keratoconus.[2] Vega-Estrada et al further identified that posterior keratometry was similar in DS to mild keratoconus, however, a lesser degree of posterior elevation was observed in the DS group.[1] This may be related to the younger mean age of the cohort with DS, small sample size or diagnostic criteria. The authors concluded that the corneal features analysed in the DS cohort were in the range of normal to mild keratoconus.[1]
We would like to further highlight some of the challenges associated with image acquisition when performing corneal topo/tomography in patients with DS. Some of the ophthalmic manifestations such as slanted and small palpebral apertures, nystagmus and strabismus can affect fixation. We have also observed additional common behavioural responses that affect fixation and alignment; patients squeezing the eyes shut in response to the examiner touching the eyelids or involuntarily opening the mouth when asked to keep the eyes wide open.
Misaligned fixation while acquiring corneal tomography images is known to result in false keratoconus features.[3] In addition to the reported overlap in corneal features in DS and ke...
The recent study by Vega-Estrada et al highlights some of the challenges in diagnosing keratoconus in Down syndrome (DS).[1] Previous studies have shown that the cornea of individuals with DS without evidence of keratoconus appear to be steeper and thinner than the general population, both being features characteristic of keratoconus.[2] Vega-Estrada et al further identified that posterior keratometry was similar in DS to mild keratoconus, however, a lesser degree of posterior elevation was observed in the DS group.[1] This may be related to the younger mean age of the cohort with DS, small sample size or diagnostic criteria. The authors concluded that the corneal features analysed in the DS cohort were in the range of normal to mild keratoconus.[1]
We would like to further highlight some of the challenges associated with image acquisition when performing corneal topo/tomography in patients with DS. Some of the ophthalmic manifestations such as slanted and small palpebral apertures, nystagmus and strabismus can affect fixation. We have also observed additional common behavioural responses that affect fixation and alignment; patients squeezing the eyes shut in response to the examiner touching the eyelids or involuntarily opening the mouth when asked to keep the eyes wide open.
Misaligned fixation while acquiring corneal tomography images is known to result in false keratoconus features.[3] In addition to the reported overlap in corneal features in DS and keratoconus, fixation misalignment combined with sub-optimal quality scans may affect the reliability and repeatability of corneal topo/tomography in this population and poses challenges in diagnosing and assessing progression of keratoconus. The latter is particularly pertinent when considering the indication for corneal collagen cross-linking in patients with DS. Vega-Estrada et al have very usefully highlighted the limitations in diagnosis of keratoconus in DS and contributed to the resolution of this important issue.[1]
References
1. Vega-Estrada A, Fariselli C, Alio JL. Posterior corneal features in patients with down syndrome and their relation with keratoconus. Br J Ophthalmol Published Online First: 2 Mar 2020. doi:10.1136/bjophthalmol-2019-314939.
2. Alio JL, Vega-Estrada A, Sanz P, et al. Corneal morphologic characteristics in patients with down syndrome. JAMA Ophthalmol 2018;136:971-8.
3. Belin MW, Khachikian SS. An introduction to understanding elevation‐based topography: how elevation data are displayed–a review. Clin Exp Ophthalmol 2009;37:14-29.
Synopsis:
Applying Pearson r to assesses the repeatability of a test is a methodologic mistake which leads to misinterpretation.
Repeatability of automated leakage quantification and microaneurysm identification utilising an analysis platform for ultra-widefield fluorescein angiography. Avoid misinterpretation
Dear editor, We were interested to read the paper by Jiang A et al. published in Apr 2020 edition of the Br J Ophthalmol.1 Ultra-wide field fluorescein angiography (UWFA) provides unique opportunities for panretinal assessment of retinal diseases. The objective quantification of UWFA features is a labour-intensive manual process, limiting its utility. The authors aimed to assesses the consistency/repeatability of an automated assessment platform for the characterization of retinal vascular features, quantification of microaneurysms (MA) and leakage foci in UWFA images. For each eye, two arteriovenous-phase images and two late-phase images were selected. Automated assessment was performed for retinal vascular features, MA identification and leakage segmentation. Panretinal and zonal assessment of metrics was performed. The authors mentioned a significant correlation between paired time points for retinal vessel area and vessel length on early images (Pearson r=0.92, p<0.0001; Pearson r=0.94, p<0.0001) and late images (Pearson r=0.92, p<0.0001; Pearson r=0.92, p<0.0001, respectively). Panretinal and zonal MA counts demonst...
Synopsis:
Applying Pearson r to assesses the repeatability of a test is a methodologic mistake which leads to misinterpretation.
Repeatability of automated leakage quantification and microaneurysm identification utilising an analysis platform for ultra-widefield fluorescein angiography. Avoid misinterpretation
Dear editor, We were interested to read the paper by Jiang A et al. published in Apr 2020 edition of the Br J Ophthalmol.1 Ultra-wide field fluorescein angiography (UWFA) provides unique opportunities for panretinal assessment of retinal diseases. The objective quantification of UWFA features is a labour-intensive manual process, limiting its utility. The authors aimed to assesses the consistency/repeatability of an automated assessment platform for the characterization of retinal vascular features, quantification of microaneurysms (MA) and leakage foci in UWFA images. For each eye, two arteriovenous-phase images and two late-phase images were selected. Automated assessment was performed for retinal vascular features, MA identification and leakage segmentation. Panretinal and zonal assessment of metrics was performed. The authors mentioned a significant correlation between paired time points for retinal vessel area and vessel length on early images (Pearson r=0.92, p<0.0001; Pearson r=0.94, p<0.0001) and late images (Pearson r=0.92, p<0.0001; Pearson r=0.92, p<0.0001, respectively). Panretinal and zonal MA counts demonstrated high repeatability between images (all p<0.0001). The automated MA algorithm demonstrated a high level of precision/repeatability across multiple metrics. Panretinal MA count demonstrated high repeatability between images (Pearson r=0.94, p<0.0001).
We want to congratulate the authors for this successful article, and make some contributions. Reproducibility (repeatability or reliability) can be evaluated by various statistical tests, such as Pearson r which is one of the common errors in reliability analysis. Pearson r only evaluates the linearity between two continuous variables. Any shift in the location and/or scale of a regression line leading to non-reproducibility cannot be detected by Pearson correlation coefficients (Fig. 1). 2 It is important to know that the mean value of a quantitative variable can be similar in absolute value; however, to assess reproducibility, the Pearson is not an appropriate test. Because the Pearson correlation coefficient can only assess linear association between two quantitative variables. It means, it is possible to have linear association between two variables with no reliability at al. 2 Therefore, for quantitative variables, the Intraclass Correlation Coefficient (ICCC) is one of the appropriate statistical tests for evaluating precision/repeatability. Moreover, in repeatability analysis, the approach should be individual-based, rather than global average. Pearson r cannot cover this approach. Briefly, to assess reliability, for quantitative variables, the Intraclass Correlation Coefficient (ICCC) and Bland-Altman plot are suggested. 2-6 Authors concluded that This automated algorithm demonstrated very strong intrastudy correlation between paired time points in the same phases of the angiogram for quantifying retinal vascular characteristics, MA count and leakage parameters in UWFA images. Such conclusion may be due to inappropriate use of statistical test which ultimately leads to a misleading message. So, due to inappropriate use of statistical tests (Pearson r) there may be a high level of uncertainty for their conclusion.
KEYWORDS: diagnostic tests/investigation; imaging; retina
Contributors: SS and FG drafted and revised the manuscript. SS provided conception for the project. All authors provided significant effort in the interpretation, reviewing the manuscript, final approval of the
manuscript and agreed to be accountable for all aspects of the work.
Funding: None
Competing interests: SS and FG have no competing interest
Patient consent for publication: Not required.
Ethics approval: N/A
Data availability statement: N/A.
References:
1 Jiang A, Srivastava S, Figueiredo N, et al. Repeatability of automated leakage quantification and microaneurysm identification utilising an analysis platform for ultra-widefield fluorescein angiography. Br J Ophthalmol. 2020;104:500-503.
2 Szklo M, Nieto FJ. Epidemiology beyond the basics. 3rd ed. Manhattan: Jones and Bartlett Publisher, United State, 2014.
3 Sabour S. Reproducibility of semi-automatic coronary plaque quantification in coronary CT angiography with sub-mSv radiation dose; common mistakes. J Cardiovasc Comput Tomogr. 2016; 10:21-2.
4 Sabour S. Reproducibility of the external surface position in left-breast DIBH radiotherapy with spirometer-based monitoring: methodological mistake. J Appl Clin Med Phys. 2014;15:4909.
5 Sabour S. Reliability of automatic vibratory equipment for ultrasonic strain measurement of the median nerve: common mistake. Ultrasound Med Biol. 2015; 41:1119-20.
6 Sabour S, Ghassemi F. Accuracy, validity, and reliability of the infrared optical head tracker (IOHT). Invest Ophthalmol Vis Sci. 2012;53:4776.
Figure 1: Cases when Pearson correlation coefficient fails to detect non reproducibility
At the outset, we would like to congratulate the authors for determining the presence of the viral RNA over time in conjunctival specimens of a patient with COVID-19, which was much needed.
The clinical course of viral conjunctivitis is self-limiting. Usually only supportive treatments like cold compress, artificial tears and topical steroids are given. The time duration taken for symptoms to subside without treatment ranges from 4-6 days to 2-3 weeks, depending upon the type of disease.[1] Clinical studies regarding the usage of antivirals for conjunctivitis reveal that they were effective only for DNA viruses and was not free of toxicity.[2]
In the case report regarding ocular manifestation of patient with 2019 novel corona virus disease,[3] the ocular symptoms of patient resolved after 5 days of its onset and the author claims it to be possibly due to treatment with ribavirin eye drops. As Corona virus is a RNA virus, we believe that antiviral therapy would have been limited use. Adequate corneal tissue levels of antiviral agents are achieved by both topical and systemic administration.[4] If antiviral therapy was the reason for improvement of ocular symptoms, the patient was on three oral antiviral drugs (Umifenovir, lopinavir and ritonavir) in addition to topical ribavirin. Therefore, attributing only topical ribavirin for curing ocular symptoms may not be appropriate with the limited evidence.
The authors also had mentioned that sterile synthetic f...
At the outset, we would like to congratulate the authors for determining the presence of the viral RNA over time in conjunctival specimens of a patient with COVID-19, which was much needed.
The clinical course of viral conjunctivitis is self-limiting. Usually only supportive treatments like cold compress, artificial tears and topical steroids are given. The time duration taken for symptoms to subside without treatment ranges from 4-6 days to 2-3 weeks, depending upon the type of disease.[1] Clinical studies regarding the usage of antivirals for conjunctivitis reveal that they were effective only for DNA viruses and was not free of toxicity.[2]
In the case report regarding ocular manifestation of patient with 2019 novel corona virus disease,[3] the ocular symptoms of patient resolved after 5 days of its onset and the author claims it to be possibly due to treatment with ribavirin eye drops. As Corona virus is a RNA virus, we believe that antiviral therapy would have been limited use. Adequate corneal tissue levels of antiviral agents are achieved by both topical and systemic administration.[4] If antiviral therapy was the reason for improvement of ocular symptoms, the patient was on three oral antiviral drugs (Umifenovir, lopinavir and ritonavir) in addition to topical ribavirin. Therefore, attributing only topical ribavirin for curing ocular symptoms may not be appropriate with the limited evidence.
The authors also had mentioned that sterile synthetic fibre swab was used for conjunctival swabs. It would be better if additional details regarding the material of swab stick and the technique were mentioned. This will also help other researchers for precise isolation and detection of the virus. Moreover, authors have mentioned a study by Xia et al, where out of 30 patients only one patients swab had come positive.[5] This highlights the skill in the authors technique.
Reference:
1 Bialasiewicz A. Adenoviral Keratoconjunctivitis. Sultan Qaboos Univ Med J 2007;7:15–23.
2 Skevaki CL, Galani IE, Pararas MV, et al. Treatment of viral conjunctivitis with antiviral drugs. Drugs 2011;71:331–47. doi:10.2165/11585330-000000000-00000
3 Chen L, Liu M, Zhang Z, et al. Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol Published Online First: 7 April 2020. doi:10.1136/bjophthalmol-2020-316304
4 Dias C, Nashed Y, Atluri H, et al. Ocular penetration of acyclovir and its peptide prodrugs valacyclovir and val-valacyclovir following systemic administration in rabbits: An evaluation using ocular microdialysis and LC-MS. Curr Eye Res 2002;25:243–52. doi:10.1076/ceyr.25.4.243.13488
5 Xia J, Tong J, Liu M, et al. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J Med Virol Published Online First: 26 February 2020. doi:10.1002/jmv.25725
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.
This is an informative article highlighting the difficulties in diagnosing optic nerve hypoplasia (ONH) in infants. Comparisons were made of the reliability of MRI orbit to that of fundal photography, with the authors concluding that the latter was superior to neuroimaging for diagnostic purposes. Whilst valid, this may imply that MRI brain scans are not indicated when a diagnosis of ONH is under consideration.
ONH has an incidence of between 2-10.9 per 100,000 births, systemic associations include developmental delay and neurologic deficits in over 50% and endocrine dysfunction in just over one-quarter of patients.(1) Children may display midline structural defects (abnormalities of the septum pellucidum, corpus callosum and pituitary axis), in addition to other cortical abnormalities, thus requiring neuroimaging.(1,2) A diagnosis of septo-optic dysplasia becomes appropriate when two out of three features are present: ONH, midline abnormalities and pituitary insufficiency. As babies and infants with ONH present primarily with abnormal visual behaviour, nystagmus, strabismus or amblyopia, from as early as 3 months of age, the Ophthalmologist may be the first specialist to evaluate the patient, and so the importance of investigating the wider clinical and radiological features cannot be overstated. This was not mentioned in this paper by Kruglyakova et al.
Whilst one can argue that a normal MRI brain scan in a child with ONH is not predictive of future end...
This is an informative article highlighting the difficulties in diagnosing optic nerve hypoplasia (ONH) in infants. Comparisons were made of the reliability of MRI orbit to that of fundal photography, with the authors concluding that the latter was superior to neuroimaging for diagnostic purposes. Whilst valid, this may imply that MRI brain scans are not indicated when a diagnosis of ONH is under consideration.
ONH has an incidence of between 2-10.9 per 100,000 births, systemic associations include developmental delay and neurologic deficits in over 50% and endocrine dysfunction in just over one-quarter of patients.(1) Children may display midline structural defects (abnormalities of the septum pellucidum, corpus callosum and pituitary axis), in addition to other cortical abnormalities, thus requiring neuroimaging.(1,2) A diagnosis of septo-optic dysplasia becomes appropriate when two out of three features are present: ONH, midline abnormalities and pituitary insufficiency. As babies and infants with ONH present primarily with abnormal visual behaviour, nystagmus, strabismus or amblyopia, from as early as 3 months of age, the Ophthalmologist may be the first specialist to evaluate the patient, and so the importance of investigating the wider clinical and radiological features cannot be overstated. This was not mentioned in this paper by Kruglyakova et al.
Whilst one can argue that a normal MRI brain scan in a child with ONH is not predictive of future endocrinopathy (3), the importance of evaluation by the Paediatric team should not be lost to the readers. One fears that the message the reader may fail to grasp is that at the time of diagnosis, an opportunity presents itself for the Ophthalmologist to include the wider paediatric multidisciplinary team to investigate and manage potential endocrine and neurodevelopmental complications, which are common in children with this congenital ocular defect.(4)
References
1. Mohney BG, Young RC, Diehl N. Incidence and associated endocrine and neurologic abnormalities of optic nerve hypoplasia. JAMA Ophthalmol. 2013 Jul;131(7):898-902.
2. Webb EA, Dattani MT. Septo-optic Dysplasia. Eur J Hum Genet. 2010 Apr;18(4):393-7.
3. Qian X, Fouzdar Jain S, Morgan LA, Kruse T, Cabrera M, Suh DW. Neuroimaging and endocrine disorders in paediatric optic nerve hypoplasia. Br J Ophthalmol. 2018 Jul;102(7):906-910.
4. Parr JR, Dale NJ, Shaffer LM, Salt AT. Social communication difficulties and autism spectrum disorder in young children with optic nerve hypoplasia and/or septo-optic dysplasia. Dev Med Child Neurol. 2010 Oct;52(10):917-21.
Optic disc drusen pose a diagnostic challenge when trying to differentiate between papilloedema and pseudopapilloedema.1 Dahlman-Noor et al highlight the importance of a structured history when evaluating children with optic nerve head (ONH) swelling. The authors recommend a future study to explore the diagnostic accuracy of an algorithm published by the Royal College of Paediatrics and Child Health (RCPCH) which details key features of the history (e.g. headache, vomiting, visual symptoms) that should trigger neuroimaging.2
As part of a prospective study of children referred to our regional paediatric ophthalmology service for assessment for ONH swelling, we implemented this algorithm. 122 children under 16 years of age were assessed from 1st January to 31st December 2018. 93% (113/122) had optic disc drusen, 4% (5/122) had normal optic discs, and 3% (4/122) had papilloedema. Two cases of papilloedema were caused by idiopathic intracranial hypertension (IIH) and two by venous sinus thrombosis.
Of the 118 patients with drusen or normal discs, only one fulfilled the RCPCH criteria for neuroimaging: a 14-year-old girl with persistent headaches and vomiting. Neuroimaging and lumbar puncture were unremarkable, and her symptoms were ultimately attributed to migraine.
For the four patients with papilloedema, the algorithm-derived questions would have triggered neuroimaging in three cases. This yields a specificity of 99% but a sensitivity of only...
Optic disc drusen pose a diagnostic challenge when trying to differentiate between papilloedema and pseudopapilloedema.1 Dahlman-Noor et al highlight the importance of a structured history when evaluating children with optic nerve head (ONH) swelling. The authors recommend a future study to explore the diagnostic accuracy of an algorithm published by the Royal College of Paediatrics and Child Health (RCPCH) which details key features of the history (e.g. headache, vomiting, visual symptoms) that should trigger neuroimaging.2
As part of a prospective study of children referred to our regional paediatric ophthalmology service for assessment for ONH swelling, we implemented this algorithm. 122 children under 16 years of age were assessed from 1st January to 31st December 2018. 93% (113/122) had optic disc drusen, 4% (5/122) had normal optic discs, and 3% (4/122) had papilloedema. Two cases of papilloedema were caused by idiopathic intracranial hypertension (IIH) and two by venous sinus thrombosis.
Of the 118 patients with drusen or normal discs, only one fulfilled the RCPCH criteria for neuroimaging: a 14-year-old girl with persistent headaches and vomiting. Neuroimaging and lumbar puncture were unremarkable, and her symptoms were ultimately attributed to migraine.
For the four patients with papilloedema, the algorithm-derived questions would have triggered neuroimaging in three cases. This yields a specificity of 99% but a sensitivity of only 75%.
One patient with IIH did not fulfil the criteria for neuroimaging. This 13-year-old girl was asymptomatic despite having marked bilateral optic disc swelling and raised intracranial pressure. The ONH abnormalities were identified on routine optometric examination.
The high specificity of the RCPCH algorithm indicates that when the screening questions are positive, it is likely that a child has intracranial pathology and neuroimaging is justified. However, in our cohort, the sensitivity was insufficient for the algorithm to act as a screening tool in isolation.
1. Chang MY, Velez FG, Demer JL, et al. Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema. Ophthalmology. 2017;124(12):1839-1848.
2. Walker D, Grundy R, Kennedy C et al. The diagnosis of brain tumours in children. www.rcph.ac.uk/bpp.
Dear Editor,
We have read the review article entitled “Ocular complications of cat scratch disease” Johnson A. Br J Ophthalmol 2020;0:1-7. We want to congratulate the author for this important review article, and make some contributions.
In the review article, it has been indicated that optical coherence tomography (OCT) imaging is of value to monitoring cat scratch disease (CSD), particularly for neuroretinitis and multifocal retinitis.
We would like to highlight a feature of focal retinitis with spectral domain optical coherence tomography (SD-OCT). Small areas of retinitis, less than 500 microns in diameter, can be seen on OCT imaging. These appear as areas of focal hyper-reflectivity of the inner retinal layers and decreased reflectivity causing a shadow on the outer retinal layers and choroid. This was seen in two patients presenting to our service recently with Bartonella henselae CSD diagnosed clinically and confirmed by positive serology.
The first case was a 49-year-old Caucasian male who presented with bilateral inflammatory papillitis and multifocal retinitis without a macular star, confirmed with serology as Bartonella henselae (IgG >2048). He had good presenting Snellen visual acuities of 6/5 right, 6/6 left. OCT imaging at acute presentation showed multifocal retinitis seen as small areas retinal hyper-reflectivity of the inner retina with outer retinal disruption. The disease resolved without treatment in 8 months, with...
Show MoreDear Editor,
Show MoreWe read with great interest the excellent paper by Sagiv and collegues Ocular preservation with neoadjuvant Vismodegib in patients with locally advanced periocular basal cell carcinoma.1
The article is a great contribution for a topic with a growing, but still limited worldwide experience. Our interest is to discuss the surgical approach after neoadjuvant Vismodegib.
The authors present a patient with a 5x4cm locally advanced periocular basal cell carcinoma (LAP-BCC) with small nerve perineural invasion (>0.1mm) involving lower eyelid, inner canthus and cheek. The patient showed a significant response after 10 months of Vismodegib. Anyhow, it was clearly a partial response with 3 suspicious areas of BCC after treatment. The authors decided to treat separately each area with surgery, and histology (en face sections) confirmed the presence of tumor in two. The reconstructive outcome was excellent, and at the time of publication the patient was free of disease, 11 months after surgery.
We agree with the authors, when they consider as a limitation the fact that “surgery did not always include the entire area of the original tumor”.
Most studies involving smoothened inhibitors thus far have measured clinical tumor shrinkage but not true histologic margin control. Even after a complete clinical response (CCR), there is no way to assure that it will result in a complete histological clearance (CHR).
Several authors discussed thi...
To the Editor,
We appreciate the authors' interest in our study. In their letter to the editor regarding our meta-analysis[1], the authors raise an issue regarding the inclusion of the diseases in the two groups i.e. limbal stem cell deficiency (LSCD) and ocular surface disease (OSD). We adhered to the categorization of the diseases as indicated or mentioned in the publications which were included in the meta-analysis. Our literature search based on combinations of various “key-words” or “key-terms” returned results as depicted in the categorization of the diseases in the study.[2,3] LSCD being a sub-set of OSD, has signs and symptoms in common with many other conditions, hence it was important that the term “limbal stem cell deficiency” appeared in the publications for the study participants to be categorized into the LSCD group.[2,3,4]
The lack of consideration of the severity of LSCD and OSD was unavoidable due to the limited data within the source publications. It is apparent that the severity of the disease may affect the corneal epithelial basal cell density (BCD) and nerve fibre parameters.[5,6] The lack of data is likely explained by the difficulty in imaging in the more severe disease when corneal transparency is reduced; the corneal basal cells and nerves are difficult to image using confocal microscopy when the cornea is not clear. This is an important factor which is highlighted in our study.[1] Furthermore, our analysis did not attempt to c...
Show MoreDear Editor,
We read the article published by Chaudhary, et al (1) with great interest and laud them on the quality and design of their study. Primary congenital blindness (PCG) poses a challenge to clinicians, both in terms of diagnosis, and treatment. (2)
We would like to bring to the authors’ notice a similar study conducted in 2017 (3) of 230 eyes of 121 PCG patients having undergone a primary CTT. This study differed from the present study in the fact that it had a longer average follow-up period of 28.87 years with a more concentrated follow-up range of 21.5-38 years. There were also two main differences in the findings of the two studies.
Contrary to the results in the present study where the infants with PCG fared better than the neonates (48.9% >6/60), the previous study found that 76.3% newborns with PCG had a vision better than 6/60. Additionally, the previous study, found visual acuity to be better than 6/60 in a greater proportion of patients (76.1%) at the last follow-up, as compared to the proportion in the study by Chaudhary et al (55.3%). Applying the WHO recommendation of measuring vision in the better eye, (4) the results improved to 89.3% in the study by Sood et al. (3)
A possible reason for these disparities between the studies could be the difference in presentation times of the patients and the study inclusion criteria. While the present study reports late presentation, over half of the patients (53%) in the earlier pub...
Show MoreThe recent study by Vega-Estrada et al highlights some of the challenges in diagnosing keratoconus in Down syndrome (DS).[1] Previous studies have shown that the cornea of individuals with DS without evidence of keratoconus appear to be steeper and thinner than the general population, both being features characteristic of keratoconus.[2] Vega-Estrada et al further identified that posterior keratometry was similar in DS to mild keratoconus, however, a lesser degree of posterior elevation was observed in the DS group.[1] This may be related to the younger mean age of the cohort with DS, small sample size or diagnostic criteria. The authors concluded that the corneal features analysed in the DS cohort were in the range of normal to mild keratoconus.[1]
We would like to further highlight some of the challenges associated with image acquisition when performing corneal topo/tomography in patients with DS. Some of the ophthalmic manifestations such as slanted and small palpebral apertures, nystagmus and strabismus can affect fixation. We have also observed additional common behavioural responses that affect fixation and alignment; patients squeezing the eyes shut in response to the examiner touching the eyelids or involuntarily opening the mouth when asked to keep the eyes wide open.
Misaligned fixation while acquiring corneal tomography images is known to result in false keratoconus features.[3] In addition to the reported overlap in corneal features in DS and ke...
Show MoreSynopsis:
Applying Pearson r to assesses the repeatability of a test is a methodologic mistake which leads to misinterpretation.
Repeatability of automated leakage quantification and microaneurysm identification utilising an analysis platform for ultra-widefield fluorescein angiography. Avoid misinterpretation
Show MoreDear editor, We were interested to read the paper by Jiang A et al. published in Apr 2020 edition of the Br J Ophthalmol.1 Ultra-wide field fluorescein angiography (UWFA) provides unique opportunities for panretinal assessment of retinal diseases. The objective quantification of UWFA features is a labour-intensive manual process, limiting its utility. The authors aimed to assesses the consistency/repeatability of an automated assessment platform for the characterization of retinal vascular features, quantification of microaneurysms (MA) and leakage foci in UWFA images. For each eye, two arteriovenous-phase images and two late-phase images were selected. Automated assessment was performed for retinal vascular features, MA identification and leakage segmentation. Panretinal and zonal assessment of metrics was performed. The authors mentioned a significant correlation between paired time points for retinal vessel area and vessel length on early images (Pearson r=0.92, p<0.0001; Pearson r=0.94, p<0.0001) and late images (Pearson r=0.92, p<0.0001; Pearson r=0.92, p<0.0001, respectively). Panretinal and zonal MA counts demonst...
At the outset, we would like to congratulate the authors for determining the presence of the viral RNA over time in conjunctival specimens of a patient with COVID-19, which was much needed.
Show MoreThe clinical course of viral conjunctivitis is self-limiting. Usually only supportive treatments like cold compress, artificial tears and topical steroids are given. The time duration taken for symptoms to subside without treatment ranges from 4-6 days to 2-3 weeks, depending upon the type of disease.[1] Clinical studies regarding the usage of antivirals for conjunctivitis reveal that they were effective only for DNA viruses and was not free of toxicity.[2]
In the case report regarding ocular manifestation of patient with 2019 novel corona virus disease,[3] the ocular symptoms of patient resolved after 5 days of its onset and the author claims it to be possibly due to treatment with ribavirin eye drops. As Corona virus is a RNA virus, we believe that antiviral therapy would have been limited use. Adequate corneal tissue levels of antiviral agents are achieved by both topical and systemic administration.[4] If antiviral therapy was the reason for improvement of ocular symptoms, the patient was on three oral antiviral drugs (Umifenovir, lopinavir and ritonavir) in addition to topical ribavirin. Therefore, attributing only topical ribavirin for curing ocular symptoms may not be appropriate with the limited evidence.
The authors also had mentioned that sterile synthetic f...
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...
This is an informative article highlighting the difficulties in diagnosing optic nerve hypoplasia (ONH) in infants. Comparisons were made of the reliability of MRI orbit to that of fundal photography, with the authors concluding that the latter was superior to neuroimaging for diagnostic purposes. Whilst valid, this may imply that MRI brain scans are not indicated when a diagnosis of ONH is under consideration.
ONH has an incidence of between 2-10.9 per 100,000 births, systemic associations include developmental delay and neurologic deficits in over 50% and endocrine dysfunction in just over one-quarter of patients.(1) Children may display midline structural defects (abnormalities of the septum pellucidum, corpus callosum and pituitary axis), in addition to other cortical abnormalities, thus requiring neuroimaging.(1,2) A diagnosis of septo-optic dysplasia becomes appropriate when two out of three features are present: ONH, midline abnormalities and pituitary insufficiency. As babies and infants with ONH present primarily with abnormal visual behaviour, nystagmus, strabismus or amblyopia, from as early as 3 months of age, the Ophthalmologist may be the first specialist to evaluate the patient, and so the importance of investigating the wider clinical and radiological features cannot be overstated. This was not mentioned in this paper by Kruglyakova et al.
Whilst one can argue that a normal MRI brain scan in a child with ONH is not predictive of future end...
Show MoreOptic disc drusen pose a diagnostic challenge when trying to differentiate between papilloedema and pseudopapilloedema.1 Dahlman-Noor et al highlight the importance of a structured history when evaluating children with optic nerve head (ONH) swelling. The authors recommend a future study to explore the diagnostic accuracy of an algorithm published by the Royal College of Paediatrics and Child Health (RCPCH) which details key features of the history (e.g. headache, vomiting, visual symptoms) that should trigger neuroimaging.2
As part of a prospective study of children referred to our regional paediatric ophthalmology service for assessment for ONH swelling, we implemented this algorithm. 122 children under 16 years of age were assessed from 1st January to 31st December 2018. 93% (113/122) had optic disc drusen, 4% (5/122) had normal optic discs, and 3% (4/122) had papilloedema. Two cases of papilloedema were caused by idiopathic intracranial hypertension (IIH) and two by venous sinus thrombosis.
Of the 118 patients with drusen or normal discs, only one fulfilled the RCPCH criteria for neuroimaging: a 14-year-old girl with persistent headaches and vomiting. Neuroimaging and lumbar puncture were unremarkable, and her symptoms were ultimately attributed to migraine.
For the four patients with papilloedema, the algorithm-derived questions would have triggered neuroimaging in three cases. This yields a specificity of 99% but a sensitivity of only...
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