eLetters

700 e-Letters

  • Goblet cells - sine qua non for conjunctival rehabilitation

    To the editor,

    We read with interest the recent publication by Bertolin et al. (“In vitro establishment, validation and characterisation of conjunctival epithelium outgrowth using tissue fragments and amniotic membrane”). Their validated conjunctival analogue of the simple limbal epithelial transplantation does represent a promising advance in the field. It is, however, interesting to note that the established tissue application was mainly validated on its growth potential and not specifically on its ability to reinstate a healthy ocular mucosal surface.

    Functional validation is of utmost importance, especially as the glued fragments are directly transplanted. This approach circumvents the need for expensive cell culture but also bypasses the stringent release criteria for cell therapies or tissue-engineered transplantation products. We would suggest that before this technique can be considered fully validated, it should be demonstrated that the obtained conjunctival cells contribute to the first line of mucosal defence, i.e. barrier formation. Several conjunctival barriers can be identified, such as intercellular junction complexes, glycocalyx and secreted mucins. Bertolin et al. demonstrated the presence of tight junctions (cfr. ZO-1 protein) and a glycocalyx (cfr. membrane-associated mucin-1), but failed to address the presence of goblet cells. As goblet cells are responsible for the secretion of mucin 5AC, which is the most abundant mucin in the mucin la...

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  • Is impaired cerebrospinal fluid dynamics the link between dementia and normal-tension glaucoma ?

    We like to congratulate Mullany et al. for their paper on normal-tension glaucoma is associated with cognitive impairment.1 To link normal-tension glaucoma (NTG) to cognitive impairment and therefore to a neurodegenerative process opens a new vista and research approach for glaucoma research. NTG indeed is an intriguing optic neuropathy that presents with a glaucomatous optic disc appearance and visual field loss similar to that seen in primary open angle glaucoma. The main risk factor for glaucoma however, increased intraocular pressure is missing.

    Unlike other cranial nerves the optic nerve is a white matter tract of the brain, enveloped in the meninges (dura, arachnoid and pia mater) and surrounded by cerebrospinal fluid (CSF) on its entire length. And CSF indeed may be the link that connects the neurodegenerative process leading to cognitive impairment and the glaucomatous optic neuropathy in NTG. Recent research demonstrated a relationship between decreased CSF flow, measured in the ventricles and the spinal cord, and cognitive deficit in the elderly.2 In NTG, impaired CSF dynamics was demonstrated with computer assisted cisternography in the subarachnoid space of the intraorbital optic nerve most pronounced in the bulbar region behind the eye globe.3 In a recent publication we found an elevated L-PGDS concentration in the subarachnoid space of the optic nerve in NTG patients with optic nerve sheath compartment syndrome that results in a reduced CSF turnover.4...

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  • Macular hole surgery should be prioritised, not delayed by observation.

    We would like to congratulate Uwaydat et al. on their large series of spontaneously closed macular holes (MH), which adds new information to the literature.(1) It reinforces the observation that traumatic MH can spontaneously close and that a period of observation in these eyes, where the results of surgery are not clear, is a worthwhile option. However, we disagree with their conclusion that eyes with recent onset small primary MHs should also be observed. The authors don’t suggest a time period for observation but found that the median time for closure for these small holes was 4.4 months.

    The report by Uwaydat et al. has 40 authors and the 60 cases of idiopathic MH were collected over at least a two-year period. Assuming a conservative number of 25 MH cases seen per surgeon per annum, this would give a spontaneous closure rate of ~3%, which is similar to the published literature as the authors review in their article.

    MH are known to enlarge with time, even in the short term. Madi et al, reported that 83% enlarged, by a median of 105 microns in 8 weeks. (2) Similarly, Berton et al recently estimated that holes less than 250 microns enlarge by a mean of 1.67 microns per day, resulting in a similar 100-micron increase in 2 months.(3)

    The anatomical and visual outcomes of surgery are dependent on MH diameter and duration. Holes greater than 300 microns, and with a duration more than four months are less likely to regain 0.3 logMAR or better.(4)...

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  • Extended Utility Domains for Health Economics Evaluations in Ophthalmology: A call to action

    Atik et al (BJOhttps://bjo.bmj.com/content/105/5/602) have done an excellent job of summarizing the current state of the art for conducting health economic evaluations in ophthalmology. Not surprisingly, however, such tools and techniques were originally designed to address broader questions of healthcare funding and resource allocation across many disparate clinical areas. As such, the general use case was very far removed from ophthalmology. This is relevant as a central component is the calculation of the utility parameters used, particularly in cost-effectiveness calculations (1). At present, the standard default utility measure remains the EQ5D, which does not prima facie include a vision specific domain (2). Rather, a “Vision Bolt-On” to the EQ5D which asks patients whether they “Have no problems seeing”; “Have some problem seeing”; or “Have extreme problems seeing” is proposed for increasing the precision of the utility score derived from patients for ophthalmic interventions (3). Unfortunately, the “Vision Bolt On” while theoretically increasing the discriminating power of the EQ-5D has not been widely adopted in economic evaluations conducted in ophthalmology (3-4). Moreover, as currently configured, the “Vision Bolt On” questions fail to adequately account for the clinical differences, say between central or fine reading vision which may be more relevant in patients with age-related macular degeneration, versus...

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  • Response to Martel et al. on visual hallucinations in sight loss

    Martel et al. report the prevalence, features and risk factors of visual hallucinations following eye removal (1). The findings indicate that visual hallucinations may be a significant and prevalent association of eye amputation, occurring in around one-third of cases. Throughout the paper, visual hallucinations are referred to as phantom visions, and categorised under the broad catchment of the phantom eye syndrome that includes pain and tactile sensations as well as visual hallucinations. Although the authors speculate phantom visions could be considered a subtype of Charles Bonnet syndrome (CBS) they are reluctant to refer to them as CBS, perhaps because of the longstanding debate as to whether CBS should be used to refer to a specific type of visual hallucination or a specific underlying cause (2,3). Where CBS is used to refer to a specific hallucination type, it is typically reserved for complex hallucinations and excludes the simple, ‘elementary’ hallucinations described as the most common experiences following enucleation. The consequence is that a range of terms have evolved to describe symptoms that have the same cause, adding confusion to the literature and hindering research and extensive efforts to raise awareness and establish appropriate patient management pathways for people with visual hallucinations (4-6).

    It is our opinion that both the simple and complex visual hallucinations described in the study should be referred to as Charles Bonnet syndrome....

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  • Re: Characteristics of endothelial corneal transplant rejection following immunisation with SARS-CoV-2 messenger RNA vaccine

    Dear Editor,

    Corneal graft rejection following vaccination was first reported in 1988 by T L Steinemann, B H Koffler and C D Jennings [1]. This article is missing from Table 1, “Summary of reported cases of corneal graft rejection”. As it is the first published study to describe this temporal association, it merits mention.

    In regards to preventative measures, we recommend thoroughly counseling patients with grafts. They should be educated on the salient warning signs of rejection including pain, redness, blurred vision, and irritation. Patients should also be informed that COVID-19 vaccination may pose a risk to the viability of their corneal grafts. We recommend prophylactically increasing topical steroids for 3-4 weeks around the time of each vaccination.

    References
    1. Steinemann TL, Koffler BH, Jennings CD. Corneal allograft rejection following immunization. Am J Ophthalmol. 1988 Nov 15;106(5):575-8. doi: 10.1016/0002-9394(88)90588-0. PMID: 3056015.

  • Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study- SAFETY Analysis

    Dear Editor,
    With great excitement, we read the original article titled “Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study” by Bulirsch et al.1 We congratulate the authors on their detailed analysis and on adding another important real world data related to brolucizumab usage. As we are still trying to understand the pathogenesis of brolucizumab related immunogenicity and the population at risk,2-4 it would be very helpful for the readers if the authors could share the following information.

    1. Were the 7 eyes in which IOI was recorded have history of any other autoimmune systemic diseases such as arthritis, thyroid abnormalities etc ?
    2. It would be helpful if the authors could clarify if the 4 eyes that had intermediate uveitis and vitreous cells underwent fluorescein angigraphy or wide filed imaging to rule out the possibility of peripheral retinal vasulilits.
    3. It would be helpful for the readers if we could know the indication of using subconjunctival dexamethasone in four cases?
    4. After treatment, were all the patients who had vitritis completely free of cells/inflammation on clinical examination or were they asymptomatic?

    Ashish Sharma, Nilesh Kumar, Nikulaa Parachuri
    Lotus Eye Hospital and Institute, Coimbatore, TN, India

    References
    1. Bulirsch LM, Saßmannshausen M, Nadal J, et al Short-term real-world outcomes following intravitreal brolucizumab for neovas...

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  • Benzalkonium chloride (BAK)-preserved anti-glaucoma drops elicits Ocular surface inflammation in naïve glaucomatous patients starting 6 months onwards

    Dear Editor:

    We welcome the recent meta-analysis by Hedengran and co-workers in the British Journal of Ophthalmology (BJO).1 This study compared the efficacy and safety of benzalkonium chloride (BAK)-preserved eye drops with alternatively preserved (AP) and preservative-free (PF) eye drops. The meta-analysis was conducted on 16 studies that range from 15 days to 6 months of study duration. Change in IOP in BAK vs AP and PF groups was meta-analysed as the primary outcome. Conjunctival hyperaemia, ocular hyperaemia, total ocular adverse effects (AE), and TBUT were also meta-analysed. The authors found no evidence of significant change in IOP and conjunctival hyperaemia between BAK vs AP and PF treatment groups. The authors concluded that the main reason for detecting no clinical differences between the groups was related to the lack of long-term clinical studies on the safety of BAK vs AP and PF eye drops. We are in consensus with Kontas AG et al., comments on the deficiencies of this meta-analysis.

    We do not agree to the conclusion, “BAK-containing and PF medications do not differ with respect to tolerability and therapy outcome”. We would like to direct the authors and readers to our recently published study in the journal, Clinical and Experimental Ophthalmology (CEO), which involved the randomised evaluation of the inflammatory effects of PF vs BAK and PF vs polyquad (PQ)-preserved eye drops in naïve glaucomatous patients over the period of 24 months.2 We p...

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  • Re: Lam et al.: Postoperative outcomes of idiopathic epiretinal membrane associated with foveoschisis

    Recently, Lam et al. [1] concluded that patients with macular pucker and foveoschisis had a higher risk of postoperative macular oedema. Since only 5/17 cases had baseline fluorescein angiography it is unclear how they distinguished foveoschisis due to tangential traction, versus cystoid macular edema (CME). Is it possible that postoperative CME was recurrent and not new? In our experience, resolution of foveoschisis takes much longer than the relatively swift resolution in 25% and partial resolution in 68.8% of cases at 1 month, so perhaps CME was a confounding factor. Indeed, Figure 3 appears more like exudative cyst than ‘foveoschisis’.

    Previous studies [2] found that nearly half of patients with macular pucker had multiple centers of retinal contraction which were associated with a higher prevalence of intraretinal cysts and greater macular thickening. Was en face OCT performed to determine the number of contraction centers and its relationship to foveoschisis as well as outcomes of surgery? Additionally, anomalous PVD with vitreoschisis [3] and vitreo-papillary adhesion [4] may be important in the pathogenesis of macular pucker. Did the authors correlate these with foveoschisis and postoperative outcomes?

    There was no significant difference in postoperative visual acuity (VA) between the foveoschisis and control groups, but this may not be the best outcome measure in macular pucker surgery. Studies [5] have shown that quantifying contrast sensitivity fu...

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  • Is it really the same?

    Dear Editor,

    In their review and meta-analysis, Hedengran and coworkers1 report no relative therapeutic benefit of preservative-free (PF) therapies over benzalkonium chloride (BAK)-preserved ones. Should the costlier PF medications therefore be abandoned, or should we question this conclusion?
    Ten of the 16 comparative trials analysed were of short duration, (between 15 and 90 days), the longest taking 6 months. Once-a-day medication was used in each trial, yet the dose response curve for BAK toxicity shows that each additional drop of BAK-containing medication doubles the likelihood of lissamine green corneal staining2 and increases the risk of early failure of glaucoma surgery.3 BAK toxicity is slow in onset increasing over time, due to its continual accumulation within ocular tissues.3 Thus, inconsistencies between experimental studies, which document the harmful effects of BAK and clinical trials, which do not, likely relate to the timing, dosing and duration of glaucoma therapy.4 Two to 12 week trials comparing BAK with alternatively preserved eyedrops, or PF formulations have shown no convincing differences in ocular tolerability, yet the benefits from switching from once-a-day preserved to PF therapy, accrue several months later.4 Longer term transition to alternatively preserved, or PF formulations improves tolerability, and there is good evidence that substituting PF tafluprost for BAK-containing latanoprost significantly improves tolerability.3 So sh...

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