Dear Editor,

We read with great interest the nice series from Sternfeld et al. about so-called “benign positional vertical opsoclonus in infants”. [1] As stated by the authors, the very specific condition they describe is not uncommon in the population, yet still poorly described in the scientific literature. Additionally, it is called differently by different authors, one reason for it being the difficulty to assess through the naked eye the very nature of the high frequency eye movements, as shown in video n°1.
The condition combines a positional tonic downgaze and abnormal vertical eye movements. Oculomotor recordings of infants presenting with this clinical picture do actually confirm that these movements comprise downbeating slow phases and upbeating saccades 2, as clinically seen in video n°2, and are therefore a vertical kind of nystagmus. We therefore proposed to refer to them as benign intermittent upbeat nystagmus in infancy. [2] As stated by the authors, the association of a tonic downgaze and an upbeat nystagmus is logical and has been related to posterior semicircular canal predominance. [3]
In addition to the evidence of slow phases in this condition and to the fact that, to the best of our knowledge, no pulse of purely vertical saccades has ever been recorded, the very possibility for the oculomotor system to produce such movements is questionable. Opsoclonus, by definition, designates a succession of multidirectional saccades. We therefore believe that the term “vertical opsoclonus” should be avoided.

1. Sternfeld A, Lobel D, Leiba H, Luckman J, Michowiz S, Goldenberg-Cohen N. Long-term follow-up of benign positional vertical opsoclonus in infants: retrospective cohort. Br J Ophthalmol. 2018; 102: 757-60.
2. Robert MP, Michel S, Adjadj E, Boddaert N, Desguerre I, Vidal PP. Benign intermittent upbeat nystagmus in infancy: a new clinical entity. Eur J Paediatr Neurol. 2015; 19: 262-5.
3. Brodsky MC, Donahue SP. Primary oblique muscle overaction: the brain throws a wild pitch. Arch Ophthalmol. 2001; 119: 1307-14.

We thank Dr. Sarnicola and family for their interest in our work and at the same time we apologize for not mentioning their preliminary results published in 2010; in this regard, some issues need be clarified.
We used an acronym to shorten the text and facilitate the readers of our article by eliminating this way long descriptive wording of the procedure. This did not imply by any means an attempt at modifying the terminology of surgical techniques, which is usually a task of the ophthalmological community. In fact, a particular acronym becomes a standard only when it is cited as such by numerous papers in the literature. This is not seeming the case, for the acronym “AVB”, that has never been used after its initial introduction by Sarnicola et al., thus failing to achieve the purpose aimed at.
In addition, we had a reason to introduce a new acronym because of a substantial difference in the surgical technique: in fact, instead of creating a new corneal tunnel into the emphysematous tissue, we inject ophthalmic viscoelastic device (OVD) in the same track created for pneumatic dissection, thus increasing surgical reproducibility and safety.
The lack of previous data we indicated (“…little data are available on the success rate…type of cleavage obtained, visual results and complications of this approach”) was simply related to the new concept of performing the injection of the OVD in the same corneal path where the air had failed.
In our series visual acuity was significantly better after big bubble-DALK than after viscobubble-DALK in the first postoperative months, suggesting a transient negative effect of the OVD; this is an original result never described in any of the papers cited by the Sarnicola et al. in addition, they classified as dDALK all those procedures with a successful pneumatic dissection, whereas we now know that most of big bubbles created with air injection are actually pre-descemetic. This has been demonstrated by several authors after the initial observation by Dua.1 This mistake due to the lack of knowledge of the true anatomy of the floor is combined with the procedural error of putting together all cases with a successful bubble creation, without distinction between those obtained with air injection and those obtained with OVD injection. Our original results show a significant difference in postoperative vision between these two subgroups and represents the main original contribution of the paper. Instead, the methodology used by the Sarnicola group leads to a completely false analysis of the results because it is based to the erroneous assumption that all successful bubbles are descemetic.

References:
1. Dua HS, Faraj LA, Said DG, et al. Human corneal anatomy redefined: a novel pre-
Descemet’s layer (Dua’s layer). Ophthalmology 2013;120:1778–85.

We thank Dr. Tobon for his comments regarding our recently published article on refractive errors frequency in Colombia.1
Initially he referred to the exclusion of the participants with less than 20/40 of distance corrected vision. The explanation of the application of this criterium was that, since as it has been shown, reproducibility of manifest refraction is less in patients with bad distance corrected visual acuity, and in this study we needed to have a very reliable manifest refraction examination.2
However, we believe that Dr. Tobon highlights a very interesting point, which is worth analyzing in more detail. Ours and other studies that have analyzed the prevalence of refractive errors in a population have excluded eyes with other ocular conditions, including amblyopia. For example, in the study conducted in Mexico by Gomez-Salazar et al, which included a very large sample (more than 670,000 patients), they excluded patients with amblyopia.3 This made it impossible to analyze the frequency of amblyopia or anisometropia.
In our study we excluded those patients with less than 20/40 of distance corrected visual acuity in any eye. Unfortunately, we did not keep the information on those patients excluded, and therefore we cannot determine the exact number or diagnosis of those cases. For future studies we will record such information.
With regard to the second query of Dr. Tobon, we decided not to use cyclopegic refraction in this study, performed around our country, because this additional intervention would have required more complex logistical necessities, ethical requirements. Since the participants would have been exposed to an additional risk,4 although small, it should have been expressly indicated in the informed consent, and accepted by the potential participants (or in the case of the children by the parents or guardians), issue that at a given moment could have decreased the confidence of the population and made it more difficult to recruit patients in certain areas of the country, distant from our usual care center, being us a group of researchers not known in those areas to which we move for the study. Instead, we decided to perform a sequential examination by experienced optometrists: first a non-cycloplegic retinoscopy, making it as static as possible by requesting the patients to keep the fixation in a distant object in order to relax the accommodation and secondly, we carried out a careful manifest refraction. The results of the latter were the one taken into account in the study. If there was a discrepancy between the retinoscopy and the manifest refraction, the optometrist rechecked the patient. As other experts have indicated (see the explanation by Marsh-Tootle and Frazier), this approach is valid, but as we recognized it, it could be considered a weakness of our study. It is correct that despite the meticulousness in performing these non-cycloplegic examinations, we could have overestimated the frequency of myopia and underestimated that of hyperopia, especially in patients with ages between 8 and 11 years.

REFERENCES

1. Galvis V, Tello A, Otero J, et al. Prevalence of refractive errors in Colombia: MIOPUR study. Br J Ophthalmol 2018;102:1320-3.
2. Leinonen J, Laakkonen E, Laatikainen L. Repeatability (test-retest variability) of refractive error measurement in clinical settings. Acta Ophthalmol Scand 2006;84:532-6.
3. Gomez-Salazar F, Campos-Romero A, Gomez-Campaña H, et al. Refractive errors among children, adolescents and adults attending eye clinics in Mexico. Int J Ophthalmol 2017;10:796-802.
4. Bhatia SS, Vidyashankar C, Sharma RK, et al. Systemic toxicity with cyclopentolate eye drops. Indian Pediatr 2000;37:329-31.
5. Marsh-Tootle WL, Frazier MG. Infants, toddlers and children. Borish's Clinical
Refraction. 2nd edn. Philadelphia: Buiterworth Heinemann Elsevier, 2006:1415–6.

Dear Editor,

We thank Drs Sabherwal and Sood for their interest in our article.(1) We would like to respond to the interesting points they raise.

Table 3 presents our analyses of potential predictors of the correct diagnosis by rural doctors of diabetic retinopathy (DR) requiring treatment. Details on a number of the characteristics assessed in this table are presented in the first paragraph of the Results section, but not, as Drs Sabherwal and Sood point out, the proportion having received didactic training. Among the 28 rural doctors, 13 (46.4%) received such training and 15 (53.6%) did not.

In the Methods, we describe in detail the training received by ophthalmologists in the CREST (Comprehensive Rural Eye Service and Training) program. As described there, only two doctors per hospital (not all of whom examined patients in the current study) could attend the didactic phase of training at the Zhongshan Ophthalmic Center (ZOC). This is due to the limited number of ophthalmologists at a typical rural Chinese county hospital, and the heavy load of clinical duties. For more doctors to have left their facilities for the two-month didactic training would not have been practical. However, all ophthalmologists participating in the CREST network and in the current study received intensive hands-on training by medical retina experts from ZOC at their own facilities, which included the diagnosis and laser treatment of diabetic retinopathy (DR) as well as the use of the United Kingdom National Health Service Diabetic Eye Screening Program (UK NHS DESP) DR grading system assessed in our study. The median number (inter-quartile range) of hands-on training sessions received in managing DR was 3 (1, 9). As mentioned in our article, CREST is a fully-funded program by Orbis International. It provides DR training well beyond what the typical rural county-level ophthalmologist in China would receive. Training in the UK NHS DESP system was comparable between non-medical graders and doctors. For these reasons, the authors would respectfully disagree with Drs Sabherwal and Sood’s suggestion that our study was biased in favour of non-medical graders. These graders achieved a level of accuracy consistent with the standards of the UK NHS DESP, and the use of non-medical graders has been recommended by bodies such as the UK Royal College of Ophthalmologists.(2)

Drs Sabherwal and Sood also indicate that our use of an arbiter may have improved the accuracy of non-medical graders and added to the expense of the program. Use of an arbiter is standard practice in the UK NHS DESP, whose protocols we follow in CREST, and in most DR screening programs of which we are aware. As noted in our article, performance of graders on those images where the grade was unchanged by arbitration remained good: the median sensitivity was 0.80, specificity was 0.98 and kappa ranged from 0.78-0.88. Use of arbitration is an inherent cost of most such programs, and will be included in our forthcoming paper on cost-effectiveness for DR screening of non-medical graders versus local ophthalmologists. It should be noted that task-shifting approaches such as the use of non-medical graders, by reducing even when they do not eliminate the role of more expensive ophthalmologists, are very likely to be more cost-effective than traditional ophthalmologist-driven approaches.

Finally, Drs Sabherwal and Sood point out 33% of images being deemed of inadequate quality as a short-coming of our program. As clearly described in the Results section of our paper, the majority of such images were “inadequate” only in the sense that a single image, rather than two as required under UK NHS DESP protocols, had been made of the eye. In fact, as we reported, the proportion of eyes to which non-medical graders were unable to assign DR grades was 3.28% (24/732).

The authors would again like to thank Drs Sabherwal and Sood for their interest in our work, and the Editors for the opportunity to clarify the interesting and important issues they have raised.

Best regards,

Helen McAneney, Martha McKenna, Tingting Chen, Miguel Angel Vazquez Membrillo, Ling Jin, Wei Xiao, Tunde Peto, Mingguang He, Ruth Hogg, Nathan Congdon

References

1. Sabherwal S, Sood I. Comments on: "Accuracy of trained rural ophthalmologists versus non-medical image graders in the diagnosis of diabetic retinopathy in rural China". Br J Ophthalmol 2018. https://bjo.bmj.com/content/102/11/1471.responses

2. The Royal College of Ophthalmologists. Improving eye health and reducing sight loss – A ‘Call to Action’ Response. Available at https://www.rcophth.ac.uk/wp-content/uploads/2016/10/RCOphth-Call-to-Act... (Accessed: 8th November 2016)