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.
We thank S N Gillan et al for their original study investigating the influence of medical student career aims on ophthalmic surgical simulator performance. The authors reported no association between medical student interest in pursuing an ophthalmic career and microsurgical task performance.
The authors recruited subjects from the medical student division of the ‘Moorfields Academy’ and deemed these subjects as students with career interests in ophthalmology. However, we suggest that a more accurate measure in determining ophthalmic career interest would be whether these students had undertaken the ‘Duke Elder exam’, an annual national undergraduate prize examination in ophthalmology, and the only specialty-specific prize examination in the UK. We believe that undertaking the ‘Duke Elder exam’ and the preparation that this involves demonstrates commitment to the ophthalmic specialty more than being a member of the ‘Moorfields Academy’. Almost 30% of candidates ranked in the top 20 in this exam eventually pursue an ophthalmic career [1].
Moreover, as the ‘Duke Elder exam’ can be taken multiple times during the course of a medical degree, it would have been particularly interesting to examine the correlation between the frequency that this exam had been taken with microsurgical task performance. However, we would also like to state that a proportion of the subjects in this study have likely undertaken the ‘Duke Elder exam’. Finally, using the ‘Duke Elder exam’...
We thank S N Gillan et al for their original study investigating the influence of medical student career aims on ophthalmic surgical simulator performance. The authors reported no association between medical student interest in pursuing an ophthalmic career and microsurgical task performance.
The authors recruited subjects from the medical student division of the ‘Moorfields Academy’ and deemed these subjects as students with career interests in ophthalmology. However, we suggest that a more accurate measure in determining ophthalmic career interest would be whether these students had undertaken the ‘Duke Elder exam’, an annual national undergraduate prize examination in ophthalmology, and the only specialty-specific prize examination in the UK. We believe that undertaking the ‘Duke Elder exam’ and the preparation that this involves demonstrates commitment to the ophthalmic specialty more than being a member of the ‘Moorfields Academy’. Almost 30% of candidates ranked in the top 20 in this exam eventually pursue an ophthalmic career [1].
Moreover, as the ‘Duke Elder exam’ can be taken multiple times during the course of a medical degree, it would have been particularly interesting to examine the correlation between the frequency that this exam had been taken with microsurgical task performance. However, we would also like to state that a proportion of the subjects in this study have likely undertaken the ‘Duke Elder exam’. Finally, using the ‘Duke Elder exam’ as a determinant of ophthalmic career interest would provide scope to undertake a multi-centre study instead of the authors’ single-centre study as the exam is undertaken by medical students from various universities across the UK.
Regardless, we thank the authors for their insightful prospective cohort study and for highlighting the potential downsides to using the EyeSi Simulator as an assessment tool for entry into ophthalmic specialty training.
REFERENCE
1. L Joshi, V A Shanmuganathan, R L Kneebone, W Amoaku. Performance in the Duke-Elder ophthalmology undergraduate prize examination and future careers in ophthalmology. Eye (Lond). 2011 Aug;25(8):1027-1033.
We read with interest the BMJ Editorial Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear1. This highlights the need for risk mitigation in the context of commonplace eye examinations using the slit-lamp biomicroscope and direct ophthalmoscope, both requiring very close proximity manoeuvres within a few centimetres of the patients’ eye, nose and mouth. Droplet spread during eye examination likely increases during these prolonged direct examination techniques. Those at most risk are trainees working in accident and emergency, opticians or acute care settings who are required to see patients presenting with “red eye” for which conjunctivitis is a common cause.
Patients with conjunctivitis can be safely manged by the non-specialist using simple observation and history enquiry2 supplemented by a phone captured image. Remote-site consultation allows further discussion allowing an eye image and clinical details to be scrutinised without the requirement for on-site attendance. Currently, clinicians use mobile phone consultations to supplement and enhance care provision and it would seem prudent to adopt this more widely to minimise risk of Covid-19 transmission which might be acquired through public transport travel, waiting room exposure or face to face consultation. Notwithstanding confidentiality issues of commonly used freeware with private image messaging capabilities e.g Whatsap...
We read with interest the BMJ Editorial Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear1. This highlights the need for risk mitigation in the context of commonplace eye examinations using the slit-lamp biomicroscope and direct ophthalmoscope, both requiring very close proximity manoeuvres within a few centimetres of the patients’ eye, nose and mouth. Droplet spread during eye examination likely increases during these prolonged direct examination techniques. Those at most risk are trainees working in accident and emergency, opticians or acute care settings who are required to see patients presenting with “red eye” for which conjunctivitis is a common cause.
Patients with conjunctivitis can be safely manged by the non-specialist using simple observation and history enquiry2 supplemented by a phone captured image. Remote-site consultation allows further discussion allowing an eye image and clinical details to be scrutinised without the requirement for on-site attendance. Currently, clinicians use mobile phone consultations to supplement and enhance care provision and it would seem prudent to adopt this more widely to minimise risk of Covid-19 transmission which might be acquired through public transport travel, waiting room exposure or face to face consultation. Notwithstanding confidentiality issues of commonly used freeware with private image messaging capabilities e.g Whatsapp, secure ophthalmology data transmission, for example “Attend Anywhere” have been evaluated in Scotland (Livingstone I personal communication) and might be usefully adopted more widely3.
Ophthalmology is one of the highest patient volume specialties with an elderly patient demographic attending for chronic age-related eye diseases often with systemic co-morbidities rendering them a high-risk vulnerable group. To our knowledge there is no consistent UK-wide policy for protecting patients or professionals from Covid-19 transmission in the eye care setting. In the current climate of escalating Covid-19 numbers we suggest remote-site diagnosis using external eye image capture and/or video-consultation to be rapidly adopted by ophthalmologists as a risk mitigating, cost-effective approach to efficient triage and remote site management for all patients with the symptoms and signs of conjunctivitis who should not be referred to on-site hospital eye services.
References
1. Li J, Lam D, Chen Y, et al. Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear. Br J Ophthalmol 2020;104(3):297-298
2. Timlin H, Butler L, Wright M. The accuracy of the Edinburgh Red Eye Diagnostic Algorithm. Eye (Lond) 2015; 29(5): 619–624
3. Poyser O, Livingstone I, Ferguson A, et al. Real-Time Tele-Ophthalmology in the Emergency Department.) Invest. Ophthalmol. Vis. Sci. 2019;60(9):6124
We read with interest Babu’s report on ‘Utility of digitally assisted vitreoretinal surgery systems (DAVS) for high volume vitreoretinal surgery centres: a pilot study’.1 As the first unit in the United Kingdom to purchase and use the NGENUITY 3D Visualization System (Alcon Laboratories, Fort Worth USA), we would like to share our experience. We assessed DAVS against analogue microscope (AM), from the Consultant surgeons’, trainees and the scrub nurses’ perspective. In our group there was a rapid adaption to the altered colours, head position and stereo vision offered by the DAVS for macular disease, with slower uptake for complex retinal detachments and trauma. In particular, we found the view and quality of image colour in macular cases to be sharp, even at high magnification, making for easier and safer membrane peels. DAVS provided a tangibly improved image quality and ease of description and teaching never previously experience by everyone present in theatre. Surgical trainees particularly benefited from better anatomical and a 3D view of the vitreoretinal pathology. Anecdotally, we tend to agree with Babu et al’s findings that the limitations lie in complex anterior segment cases, particularly with a poor red reflex, where we found the view of the posterior capsule to be compromised compared to the AM. Also, the presence of a sizeable disparity in contrast between immediately adjacent structures in the posterior segment (e.g. colobomas, asteroid hyal...
We read with interest Babu’s report on ‘Utility of digitally assisted vitreoretinal surgery systems (DAVS) for high volume vitreoretinal surgery centres: a pilot study’.1 As the first unit in the United Kingdom to purchase and use the NGENUITY 3D Visualization System (Alcon Laboratories, Fort Worth USA), we would like to share our experience. We assessed DAVS against analogue microscope (AM), from the Consultant surgeons’, trainees and the scrub nurses’ perspective. In our group there was a rapid adaption to the altered colours, head position and stereo vision offered by the DAVS for macular disease, with slower uptake for complex retinal detachments and trauma. In particular, we found the view and quality of image colour in macular cases to be sharp, even at high magnification, making for easier and safer membrane peels. DAVS provided a tangibly improved image quality and ease of description and teaching never previously experience by everyone present in theatre. Surgical trainees particularly benefited from better anatomical and a 3D view of the vitreoretinal pathology. Anecdotally, we tend to agree with Babu et al’s findings that the limitations lie in complex anterior segment cases, particularly with a poor red reflex, where we found the view of the posterior capsule to be compromised compared to the AM. Also, the presence of a sizeable disparity in contrast between immediately adjacent structures in the posterior segment (e.g. colobomas, asteroid hyalosis) impacted on DAVS image quality. What we were not expecting was the difficulty our scrub nurses would have with the DAVS. They found that the polarised glasses rendered normal stereo vision more difficult, and the tinted lenses were a challenge when working in a dimmed ambient lighting. While the surgeons quickly adapted to the novel viewing system, our nursing colleagues found it less easy to use and took longer to adapt.
Reference:
1. Babu N, Kohli P, Jena S, et al. Utility of digitally assisted vitreoretinal surgery systems (DAVS) for high-volume vitreoretinal surgery centre: a pilot study. British Journal of Ophthalmology 2020;104:432-436.
There is no unified consensus in the peripheral nerve literature regarding the optimum type of interposition nerve graft for target tissue reinnervation. There are multiple well-designed peer reviewed studies by leading experts in peripheral nerve surgery supporting the use of acellular nerve allografts (ANAs) as viable alternatives to nerve autografts at various gap lengths [1-3]. While there are no trials directly comparing the use of ANAs to nerve autografts in corneal neurotization, Avance® allografts have now become “on label” for corneal neurotization given the successful clinical outcomes reported by several tertiary care centers [4].
In comparing the study by Catapano et al. to the study by Leyngold et al. it is important to note that the average follow up in the former was 24 months whereas it was only 6 months in the latter [4,5]. In addition, 88% of the patients in the paper by Catapano et al. were under 18 years of age vs. 14% in the paper by Leyngold et al. As stated in my previous correspondence, Park et al has shown that pediatric age is correlated to improved results in corneal neurotization irrespective of the technique [6]. Catapano et al. noted continued improvement in central corneal sensation (CCS) up to two years postoperatively. The reported CCS at 6 months postoperatively was only 30.0±26.8mm with a significant number (44%) of patients in their study having CCS at or below 10mm and peripheral corneal sensation (PCS) at or below 30mm at that...
There is no unified consensus in the peripheral nerve literature regarding the optimum type of interposition nerve graft for target tissue reinnervation. There are multiple well-designed peer reviewed studies by leading experts in peripheral nerve surgery supporting the use of acellular nerve allografts (ANAs) as viable alternatives to nerve autografts at various gap lengths [1-3]. While there are no trials directly comparing the use of ANAs to nerve autografts in corneal neurotization, Avance® allografts have now become “on label” for corneal neurotization given the successful clinical outcomes reported by several tertiary care centers [4].
In comparing the study by Catapano et al. to the study by Leyngold et al. it is important to note that the average follow up in the former was 24 months whereas it was only 6 months in the latter [4,5]. In addition, 88% of the patients in the paper by Catapano et al. were under 18 years of age vs. 14% in the paper by Leyngold et al. As stated in my previous correspondence, Park et al has shown that pediatric age is correlated to improved results in corneal neurotization irrespective of the technique [6]. Catapano et al. noted continued improvement in central corneal sensation (CCS) up to two years postoperatively. The reported CCS at 6 months postoperatively was only 30.0±26.8mm with a significant number (44%) of patients in their study having CCS at or below 10mm and peripheral corneal sensation (PCS) at or below 30mm at that time. Among the three patients (43%) reported by Leyngold et al. who had corneal sensation measurements under 35mm one had a follow up of only 3 months, second patient achieved an improvement of 34mm at 10 months after surgery despite multiple medical comorbidities and extensive conjunctival scarring, and the last patient was shown to have corneal nerve regeneration on in vivo confocal microscopy, improved ocular surface and visual acuity despite a small improvement in average corneal sensation. Also, four patients in the study by Catapano et al. were found to have persistent epithelial defects (PEDs) 24 months after the surgery (21%) compared to only 1 patient (14%) reported by Leyngold et al. at 1 month postoperatively.
Finally, the authors state that they “have yet to encounter a suboptimal neurotization outcome with use of nerve autografts to route sensory axons of the great auricular nerve to the cornea” based on only two of their published cases [7]. Such a small number of cases is not sufficient to draw significant conclusions regarding clinical outcomes of their reported technique.
References:
1. Brooks DN, Weber RV, Chao JD, et al. Processed nerve allografts for peripheral nerve reconstruction: A multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions. Microsurgery. 2012 Jan; 32(1)
2. Zuniga JR, Williams F, Petrisor D. A case-and-control, multi-site, positive controlled, prospective study of the safety and effectiveness of immediate inferior alveolar nerve processed nerve allograft reconstruction with ablation of the mandible for benign pathology. J Oral Maxillofac Surg. 2017 Dec; 75(12): 2669-2681.
3. Rinker BD, Zoldos J, Weber RV, et al. Use of processed nerve allografts to repair nerve injuries greater than 25 mm in the hand. Ann Plast Surg. 2017 Jun; 78(6S Suppl 5): S292-S295. 10.1097/SAP.0000000000001037
4. Leyngold IM, Yen MT, Tian J, et al. Minimally invasive corneal neurotization with acellular nerve allograft: surgical technique and clinical outcomes. Ophthalmic Plast Reconstr Surg 2019;35:133–40.
5. Catapano J, Fung SSM, Halliday W, et al. Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation. British J Ophthalmol. 2019:bjophthalmol-2018-313042.
6. Park J, Charlson E, Leyngold IM, et al. Corneal neurotization: A review of pathophysiology and outcomes. Ophthalmic Plast Reconstr Surg. 2020; Jan 8. doi: 10.1097/IOP.0000000000001583. [Epub ahead of print]
7. Jowett N, Pineda II R. Corneal neurotisation by great auricular nerve transfer and scleral-corneal tunnel incisions for neurotrophic keratopathy. Br J of Ophthalmol. 2018 Nov 23. pii: bjophthalmol-2018-312563
It has been seventeen years since the emergence of Severe Acute Respiratory Syndrome (SARS -CoV)1 and in 2004, we reported the presence of SARS-CoV in human tears and highlighted the possibility of human transmission through tears2.
A new strain of coronavirus (2019-nCoV) has emerged recently in China.3 A recent report highlighted the possibility of transmission through tears.4 This thus serves as a timely reminder for ophthalmologists and healthcare professionals to take necessary precautions in the clinic. Furthermore, asymptomatic patients are potentially infective.3
As ophthalmologists, we sit eye-to-eye with our patients and this close proximity puts us at high risk of being exposed to such infections. When measuring intraocular pressure under topical anaesthesia, our fingers are in contact with the periocular skin or fluorescein-stained tears and it is conceivable that poor hand hygiene increases risk of disease transmission. The tips of reusable bottles of anaesthesia may also come into contact with tear fluid or eyelashes of patients at risk. Also, the use of Schirmer’s test for dry eyes or research purposes, might be sources of infection if the tear samples are not stored properly. It is thus important to ensure good hand hygiene, to wear surgical masks, and if handling infected patients, to don personal protective equipment (PPE) and goggles. It is also important to ensure proper disinfection of reusable equipment (such as tonometer tips). Alternat...
It has been seventeen years since the emergence of Severe Acute Respiratory Syndrome (SARS -CoV)1 and in 2004, we reported the presence of SARS-CoV in human tears and highlighted the possibility of human transmission through tears2.
A new strain of coronavirus (2019-nCoV) has emerged recently in China.3 A recent report highlighted the possibility of transmission through tears.4 This thus serves as a timely reminder for ophthalmologists and healthcare professionals to take necessary precautions in the clinic. Furthermore, asymptomatic patients are potentially infective.3
As ophthalmologists, we sit eye-to-eye with our patients and this close proximity puts us at high risk of being exposed to such infections. When measuring intraocular pressure under topical anaesthesia, our fingers are in contact with the periocular skin or fluorescein-stained tears and it is conceivable that poor hand hygiene increases risk of disease transmission. The tips of reusable bottles of anaesthesia may also come into contact with tear fluid or eyelashes of patients at risk. Also, the use of Schirmer’s test for dry eyes or research purposes, might be sources of infection if the tear samples are not stored properly. It is thus important to ensure good hand hygiene, to wear surgical masks, and if handling infected patients, to don personal protective equipment (PPE) and goggles. It is also important to ensure proper disinfection of reusable equipment (such as tonometer tips). Alternatively, the use of disposable equipment such as tonometer probes/cover, single-use equipment, disposable contact lenses for procedures, might eliminate the risk of viral transmission.
The emergence of this current strain coincides with the lunar new year, and we are likely to see massive people movement within China and around the world. This facilitates disease transmission and it is thus imperative to remind all healthcare professionals to practice caution when handling patients in the clinic.
References
1. World Health Organization. Severe acute respiratory syndrome (SARS): summary table of SARS cases by country on Aug 15, 2003. Available at: http://www.who.int/csr/sars/country/en/country2003_08_15.pdf. Accessed on January 24th, 2020.
2. Loon SC, Teoh SCB, Oon LLE, Se-Thoe SY, Leo YS. The severe acute respiratory syndrome coronavirus in tears. Br J Ophthalmol 2004;88:861-863.
Dr. Leyngold states we ‘fail to support [our] viewpoint with peer reviewed studies.’ Our position against the use of acellular nerve allografts (ANAs) in corneal neurotisation was grounded on robust evidence from basic science literature demonstrating their inferior performance relative to autografts for large gap nerve repair. No clinical trial comparing the two techniques exists, and in our opinion there lacks the necessary equipoise to perform such a study.
The regeneration-restrictive properties of long-segment ANAs renders them unsuitable for use in directing sensory axons to the cornea. The largest single-centre study on Avance® ANA use for peripheral nerve repair demonstrated meaningful recovery in only 54% of cases where allografts longer than 50 mm were employed [1]. Remarkably, exploitation of the suboptimal capacity of ANAs to support nerve regeneration has been proposed as a means to inhibit axon growth in the surgical management of painful neuromas [2].
In his defence of off-label use of Avance® allografts in corneal neurotisation, Dr. Leyngold cites his case-series wherein sensory improvement of 35 mm or more was documented in two of seven eyes (29%). In contrast, Catapano et al. noted sensory improvement of 35 mm or more in 16 of 18 cases (89%) where nerve autografts were employed to route healthy trigeminal sensory axons to anaesthetic corneas [3]. In our own experience, we have yet to encounter a suboptimal neurotization outcome with use of n...
Dr. Leyngold states we ‘fail to support [our] viewpoint with peer reviewed studies.’ Our position against the use of acellular nerve allografts (ANAs) in corneal neurotisation was grounded on robust evidence from basic science literature demonstrating their inferior performance relative to autografts for large gap nerve repair. No clinical trial comparing the two techniques exists, and in our opinion there lacks the necessary equipoise to perform such a study.
The regeneration-restrictive properties of long-segment ANAs renders them unsuitable for use in directing sensory axons to the cornea. The largest single-centre study on Avance® ANA use for peripheral nerve repair demonstrated meaningful recovery in only 54% of cases where allografts longer than 50 mm were employed [1]. Remarkably, exploitation of the suboptimal capacity of ANAs to support nerve regeneration has been proposed as a means to inhibit axon growth in the surgical management of painful neuromas [2].
In his defence of off-label use of Avance® allografts in corneal neurotisation, Dr. Leyngold cites his case-series wherein sensory improvement of 35 mm or more was documented in two of seven eyes (29%). In contrast, Catapano et al. noted sensory improvement of 35 mm or more in 16 of 18 cases (89%) where nerve autografts were employed to route healthy trigeminal sensory axons to anaesthetic corneas [3]. In our own experience, we have yet to encounter a suboptimal neurotization outcome with use of nerve autografts to route sensory axons of the great auricular nerve to the cornea [4].
When counselling patients on corneal neurotisation, surgeons need be aware of the considerable evidence pointing to a higher risk of procedural failure where ANAs are substituted for nerve autografts. Articles supporting ANA use should be scrutinized for declared or undeclared conflicts of interest that may influence perception of the surgical outcome.
References:
1. Leckenby JI, Furrer C, Haug L, Juon Personeni B, Vogelin E. A retrospective case series reporting the outcomes of Avance nerve allografts in the treatment of peripheral nerve injuries. Plast Reconstr Surg 2019 doi: 10.1097/prs.0000000000006485[published Online First: Epub Date]|.
2. Hong T, Wood I, Hunter DA, et al. Neuroma Management: Capping Nerve Injuries With an Acellular Nerve Allograft Can Limit Axon Regeneration. Hand 2019:1558944719849115 doi: 10.1177/1558944719849115[published Online First: Epub Date]|.
3. Catapano J, Fung SSM, Halliday W, et al. Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation. British Journal of Ophthalmology 2019:bjophthalmol-2018-313042 doi: 10.1136/bjophthalmol-2018-313042[published Online First: Epub Date]|.
4. Jowett N, Pineda Ii R. Corneal neurotisation by great auricular nerve transfer and scleral-corneal tunnel incisions for neurotrophic keratopathy. Br J Ophthalmol 2019;103(9):1235-38 doi: 10.1136/bjophthalmol-2018-312563[published Online First: Epub Date]|.
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...
Show MoreWe thank S N Gillan et al for their original study investigating the influence of medical student career aims on ophthalmic surgical simulator performance. The authors reported no association between medical student interest in pursuing an ophthalmic career and microsurgical task performance.
The authors recruited subjects from the medical student division of the ‘Moorfields Academy’ and deemed these subjects as students with career interests in ophthalmology. However, we suggest that a more accurate measure in determining ophthalmic career interest would be whether these students had undertaken the ‘Duke Elder exam’, an annual national undergraduate prize examination in ophthalmology, and the only specialty-specific prize examination in the UK. We believe that undertaking the ‘Duke Elder exam’ and the preparation that this involves demonstrates commitment to the ophthalmic specialty more than being a member of the ‘Moorfields Academy’. Almost 30% of candidates ranked in the top 20 in this exam eventually pursue an ophthalmic career [1].
Moreover, as the ‘Duke Elder exam’ can be taken multiple times during the course of a medical degree, it would have been particularly interesting to examine the correlation between the frequency that this exam had been taken with microsurgical task performance. However, we would also like to state that a proportion of the subjects in this study have likely undertaken the ‘Duke Elder exam’. Finally, using the ‘Duke Elder exam’...
Show MoreWe read with interest the BMJ Editorial Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear1. This highlights the need for risk mitigation in the context of commonplace eye examinations using the slit-lamp biomicroscope and direct ophthalmoscope, both requiring very close proximity manoeuvres within a few centimetres of the patients’ eye, nose and mouth. Droplet spread during eye examination likely increases during these prolonged direct examination techniques. Those at most risk are trainees working in accident and emergency, opticians or acute care settings who are required to see patients presenting with “red eye” for which conjunctivitis is a common cause.
Patients with conjunctivitis can be safely manged by the non-specialist using simple observation and history enquiry2 supplemented by a phone captured image. Remote-site consultation allows further discussion allowing an eye image and clinical details to be scrutinised without the requirement for on-site attendance. Currently, clinicians use mobile phone consultations to supplement and enhance care provision and it would seem prudent to adopt this more widely to minimise risk of Covid-19 transmission which might be acquired through public transport travel, waiting room exposure or face to face consultation. Notwithstanding confidentiality issues of commonly used freeware with private image messaging capabilities e.g Whatsap...
Show MoreDear Sir
We read with interest Babu’s report on ‘Utility of digitally assisted vitreoretinal surgery systems (DAVS) for high volume vitreoretinal surgery centres: a pilot study’.1 As the first unit in the United Kingdom to purchase and use the NGENUITY 3D Visualization System (Alcon Laboratories, Fort Worth USA), we would like to share our experience. We assessed DAVS against analogue microscope (AM), from the Consultant surgeons’, trainees and the scrub nurses’ perspective. In our group there was a rapid adaption to the altered colours, head position and stereo vision offered by the DAVS for macular disease, with slower uptake for complex retinal detachments and trauma. In particular, we found the view and quality of image colour in macular cases to be sharp, even at high magnification, making for easier and safer membrane peels. DAVS provided a tangibly improved image quality and ease of description and teaching never previously experience by everyone present in theatre. Surgical trainees particularly benefited from better anatomical and a 3D view of the vitreoretinal pathology. Anecdotally, we tend to agree with Babu et al’s findings that the limitations lie in complex anterior segment cases, particularly with a poor red reflex, where we found the view of the posterior capsule to be compromised compared to the AM. Also, the presence of a sizeable disparity in contrast between immediately adjacent structures in the posterior segment (e.g. colobomas, asteroid hyal...
Show MoreThere is no unified consensus in the peripheral nerve literature regarding the optimum type of interposition nerve graft for target tissue reinnervation. There are multiple well-designed peer reviewed studies by leading experts in peripheral nerve surgery supporting the use of acellular nerve allografts (ANAs) as viable alternatives to nerve autografts at various gap lengths [1-3]. While there are no trials directly comparing the use of ANAs to nerve autografts in corneal neurotization, Avance® allografts have now become “on label” for corneal neurotization given the successful clinical outcomes reported by several tertiary care centers [4].
In comparing the study by Catapano et al. to the study by Leyngold et al. it is important to note that the average follow up in the former was 24 months whereas it was only 6 months in the latter [4,5]. In addition, 88% of the patients in the paper by Catapano et al. were under 18 years of age vs. 14% in the paper by Leyngold et al. As stated in my previous correspondence, Park et al has shown that pediatric age is correlated to improved results in corneal neurotization irrespective of the technique [6]. Catapano et al. noted continued improvement in central corneal sensation (CCS) up to two years postoperatively. The reported CCS at 6 months postoperatively was only 30.0±26.8mm with a significant number (44%) of patients in their study having CCS at or below 10mm and peripheral corneal sensation (PCS) at or below 30mm at that...
Show MoreIt has been seventeen years since the emergence of Severe Acute Respiratory Syndrome (SARS -CoV)1 and in 2004, we reported the presence of SARS-CoV in human tears and highlighted the possibility of human transmission through tears2.
A new strain of coronavirus (2019-nCoV) has emerged recently in China.3 A recent report highlighted the possibility of transmission through tears.4 This thus serves as a timely reminder for ophthalmologists and healthcare professionals to take necessary precautions in the clinic. Furthermore, asymptomatic patients are potentially infective.3
As ophthalmologists, we sit eye-to-eye with our patients and this close proximity puts us at high risk of being exposed to such infections. When measuring intraocular pressure under topical anaesthesia, our fingers are in contact with the periocular skin or fluorescein-stained tears and it is conceivable that poor hand hygiene increases risk of disease transmission. The tips of reusable bottles of anaesthesia may also come into contact with tear fluid or eyelashes of patients at risk. Also, the use of Schirmer’s test for dry eyes or research purposes, might be sources of infection if the tear samples are not stored properly. It is thus important to ensure good hand hygiene, to wear surgical masks, and if handling infected patients, to don personal protective equipment (PPE) and goggles. It is also important to ensure proper disinfection of reusable equipment (such as tonometer tips). Alternat...
Show MoreDr. Leyngold states we ‘fail to support [our] viewpoint with peer reviewed studies.’ Our position against the use of acellular nerve allografts (ANAs) in corneal neurotisation was grounded on robust evidence from basic science literature demonstrating their inferior performance relative to autografts for large gap nerve repair. No clinical trial comparing the two techniques exists, and in our opinion there lacks the necessary equipoise to perform such a study.
The regeneration-restrictive properties of long-segment ANAs renders them unsuitable for use in directing sensory axons to the cornea. The largest single-centre study on Avance® ANA use for peripheral nerve repair demonstrated meaningful recovery in only 54% of cases where allografts longer than 50 mm were employed [1]. Remarkably, exploitation of the suboptimal capacity of ANAs to support nerve regeneration has been proposed as a means to inhibit axon growth in the surgical management of painful neuromas [2].
In his defence of off-label use of Avance® allografts in corneal neurotisation, Dr. Leyngold cites his case-series wherein sensory improvement of 35 mm or more was documented in two of seven eyes (29%). In contrast, Catapano et al. noted sensory improvement of 35 mm or more in 16 of 18 cases (89%) where nerve autografts were employed to route healthy trigeminal sensory axons to anaesthetic corneas [3]. In our own experience, we have yet to encounter a suboptimal neurotization outcome with use of n...
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