Recent eLetters
Displaying 241-250 letters out of 403 published
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Mohs surgery: Efficient and effective
Submit responseDear Editor
We read with interest the report of Hsuan et al.[1]
The authors present a case series of 55 patients with basal cell carcinoma on the eyelids. There are no details regarding the size or histologic subtypes of basal cell carcinoma in the results and therefore it is difficult to assess the applicability of the results to other groups of patients who may have more or less severe basal cell carcinoma. The authors make several generalizations regarding Mohs surgery that we believe are unsubstantiated and we wish to take the opportunity to clarify a few points.
1. The essence of Mohs micrographic surgery is 100% histologic frozen section margin control. There is no other technique that enables 100% margin examination, including the authors’ breadloaf section technique. Mohs micrographic surgery has 99% five-year cure rates for basal cell carcinoma because of the thorough margin examination. In distinction, standard breadloaf section technique examines approximately 0.1% of the surgical margin, with an increased potential to miss infiltrative tumor extensions. Because the breadloaf technique is least likely to accurately detect a positive margin, many surgeons employ a tangential peripheral section analysis as a means of obtaining more through examination of the margin.
2. Mohs micrographic surgery has another advantage, which is true tissue sparing. The margin of normal skin removed during Mohs micrographic surgery may be as little as one-half of 1 millimeter. When operating on the eyelid, 1 millimeter can be the difference between sacrifice and preservation of a critical structure (i.e. punctum). The authors sacrificed 2 millimeters on both sides of the skin cancer, which in some cases may have resulted in up to 3 millimeters of unnecessary skin removal. This could result in more complicated reconstruction for patients.
3. The authors state that their patients were happy to have multiple operative sessions. For patients undergoing Mohs micrographic surgery, complete tumor removal is accomplished in one session, with reconstruction performed on the same day as tumor extirpation. The inconvenience to patients associated with staged re-excision after 48 hours of histologic examination and then a final stage reconstruction 48 hours after the last histologic sample is taken should not be underestimated. Patients in general are pleased with their care based primarily with their interaction with the physicians. However, I sincerely doubt that any patient would choose three surgical interventions over five days rather than one surgical intervention with 100% margin control in one day.
4. The authors state that Mohs surgery is "too expensive". This statement is unsubstantiated. In a cost analysis by Cook and Zitelli,[2] Mohs surgery was found to similar in cost to excisional surgery and less expensive than frozen section analysis. With three potential operative encounters, the cost of staged excision of basal cell carcinoma in the United States would exceed that for Mohs micrographic surgery with reconstruction on the same day. It is also important to note that the pathologic charges are included in the Mohs surgery fee, as the Mohs surgeon functions as both the surgeon and pathologist. Therefore, pathology charges generated for multiple staged re-excisions must be included in any calculation of cost associated with staged excision.
5. The authors characterized Mohs surgery as "laborious". I would argue that one doctor performing a very efficient tissue sparing operation all in a matter of two to four hours, a typical duration for Mohs surgery and reconstruction, with the pathology included within that time frame and fee, is both cost efficient and labor efficient. Mohs surgery has been especially designed for accuracy, tissue sparing, convenience, cost efficiency, and labor efficiency.
Mohs surgeons are expert in the complete removal of complex skin cancers, particularly on the central facial area. Mohs surgeons work closely with our colleagues in oculoplastic surgery in the United States to coordinate expert reconstruction of the resultant defects. In places where Mohs surgery is less available, close communication between the surgeon and pathologist, and tangential vertical margin processing may offer a reasonable therapeutic option, although one that is more inconvenient, costly and laborious for patients and physicians alike.
References
(1) J D Hsuan, R A Harrad, M J Potts, and C Collins. Small margin excision of periocular basal cell carcinoma: 5 year results. Br J Ophthalmol 2004; 88: 358-360.
(2) Cook J, Zitelli J. Mohs micrographic surgery: a cost analysis. J Am Acad Dermatol. 1998;39:698-703.
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Classification of ocular surface burns: Author's response
Submit responseDear Editor
The eLetter by Harun et al. on "Modification of classification of ocular chemical injuries"[1] is to be commended in so far as it highlights the problems with the current Roper-Hall classification system and the difficulties it poses in evaluating outcome and efficacy of treatment modalities in ocular surface burns. As a proposed modification however, it is a retrograde step.
The three major issues with the Roper-Hall [2] classification were that it lumped all injuries with 50% or more of limbal involvement into one category, did not take into account conjunctival involvement in the actual classification and placed undue emphasis on the degree of corneal haze.
The proposed modification by Harun S et al. goes a step backwards by grouping all injuries with more than 33% limbal involvement (1/3) into one category. The grading of a patient with all 12-clock hours of limbus involvement would then be the same as one with just over 3 clock hours of limbus involvement! The prognosis given to these two patients cannot be the same, given that the Roper-Hall and the Dua, King and Joseph [3] classifications are prognostic classifications. Furthermore, a patient presenting with less than one third limbus involvement does not necessarily come with less than one third conjunctival involvement, which could be much more. The proposed modification does not allow for such variances, which are frequent. The Dua, King and Joseph classification has the flexibility to allow for such variables and also to progressively document change both improvement and deterioration, over the acute phase of the injury. The authors rightly point out that the degree of ischaemia does not always correspond to degree of limbal involvement. Yet limbal involvement without ischaemia, in the form of loss of stem cells, can have an equally important impact on prognosis. That is precisely why the Dua, King and Joseph classification considers limbal involvement (to encompass ischaemia as well) rather than limbal ischaemia alone.
The point about conjunctival involvement is well made in the proposed modification. This does not differ significantly from the Dua, King and Joseph classification. The latter was the first to take this aspect of burns into account in determining severity and prognosis. The authors mention the importance of tarsal conjunctival involvement. This is a valid though often an impractical consideration. Associated swelling, induration, thickening, shrinkage and the like, of the lids make tarsal conjunctival evaluation impractical if not impossible in some cases, in the immediate post injury period. It was for this practical consideration that the Dua, King and Joseph classification included only the extent of bulbar conjunctival involvement in determining the grade. It is interesting to note that the authors disregard limbal fluorescein staining as an indicator of limbal damage (as proposed in the Dua, King and Joseph classification) but propose fluorescein staining as an indicator of conjunctival damage in evaluating extent of conjunctival damage. This implies that fluorescein staining is appropriate to evaluate both conjunctival epithelial damage and conjunctival ischaemia but not limbal epithelial damage and limbal ischaemia. There is no rationale for this.
Corneal haze can be an indicator of the offending chemical rather than the severity of the insult. It is not uncommon to find a clear and transparent cornea, which is totally denuded of its epithelium, immediately after a chemical injury. This can stay so for a few days before becoming rapidly hazy or opaque, or remain clear and become re- epithelised. Corneal endothelial damage leading to stromal edema and haze can occur later in the course of an acute chemical injury. Conversely, a hazy cornea with a resultant scar could do well following a corneal graft procedure if the limbal involvement is minimal. The proposed modification retains corneal haze as a grading parameter and includes a hazy cornea in grade 3 only. There are many chemical injuries, which involve 3 to 6 clock hours of the limbus (30 to 50%) with a clear cornea. These do not fall well in any grade in the proposed new classification and highlight the inherent problem in the Roper-Hall classification and its proposed modification.
Most important of all, the proposed classification is purely theoretical and has not been validated. The Dua, King and Joseph classification is based on several years of clinical experience of managing burns including over 67 patients. It is simple and easy to use (clock hours of limbus involvement and percentage of conjunctival involvement), flexible and allows for all combinations of different extents of involvement of the two structures. It is validated as a prognostic indicator and allows for accurate comparison of cases. The proposed new classification/modification fails on all these counts.
References
(1) Harun S et al. Modification of classifiaction of ocular chemical injuries [electronic response to Dua et al. A new classification of ocular surface burns] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/85/11/1379#219
(2) Roper-Hall MJ. Thermal and chemical burns. Trans Ophthalmol Soc UK 1965;85:631-53
(3) Dua HS, King AJ, Joseph A. New Classification of Ocular surface burns. Br J Ophthalmol 2001; 85:1379-83
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Modification of classifiaction of ocular chemical injuries
Submit responseDear Editor
A recent paper by Kobayashi and co-workers[1] on temporary amniotic membrane patching for acute chemical burns highlights the difficulty in the consistent classification of this type of injury.
Roper-Hall’s classification of acute chemical injuries to the eye is based on the original classification of Ballen[4] and there is little difference between them. However, in neither classification is the grade based on the most severe sign. This immediately leads to the problem of trying to classify an eye having, for example, corneal signs of one grade and conjunctival signs of another. There is also difficulty in grading the conjunctival and limbal injuries.
Dua et al.[2] recognized the problem of assessing limbal stem cell damage and proposed a quasi-analogue scale in order to incorporate inter-grade variations. They suggested using limbal fluorescein staining as a marker of limbal stem cell damage. However, their grading scheme is complex and departs significantly from that of Roper-Hall. Although fluorescein staining is a useful sign, it does not necessarily imply limbal stem cell damage or failure and has not been shown to be a better index of limbal damage than perilimbal ischaemia. Importantly, it is also becoming apparent, that both the fornices and mucocutaneous junction of the conjunctiva are important for conjunctival regeneration.[5,6] In fact, Roper Hall stressed the importance of involvement of contiguous area of the conjunctiva, which may lead to symblepharon formation.[2]
Although there are limitations with Roper-Hall’s classification, it is simple and remains popular. Rather than replace Roper-Hall and Ballen’s classification,[3] we suggest a modification, which addresses some of the issues raised and makes the classification more robust.
One of the questions that needs to be answered is whether to base the grade of injury upon the most severe sign or on a combination of ocular surface signs. A combination of signs using 3 parameters (cornea, limbus and conjunctiva) each with 3 levels requires 27 possible combinations to avoid cross-over. To avoid this complexity and without evidence to indicate a difference in prognosis, it would seem reasonable therefore to base the grade of injury on the most severe sign.
Although limbal ischaemia does not necessarily imply limbal stem cell failure, it remains to be shown that it is less indicative than fluorescein limbal staining of limbal damage. We propose therefore to continue to use limbal ischaemia in the grading of injury. With regard to conjunctival involvement, in order to be able to include the total area of involvement, we suggest dividing the conjunctival surface into bulbar and tarsal areas, as is natural. The bulbar and tarsal conjunctiva comprise approximately two thirds and one third of the total conjunctival surface respectively. Using conjunctival fluorescein staining as an indicator of the extent of conjunctival damage, the area of involvement can be based on the fraction of the third involved, limiting any division into not less than sixths. That is, the tarsal surfaces together comprise a third of conjunctiva (see Figure 1). This includes the issue that a vertical distribution of conjunctival injury is as important as a horizontal distribution.
Figure1 Estimation of Conjunctival injury
E.g, 1/6th +1/6th = 1/3rd
Corneal involvement in terms of prognosis remains an area of difficulty. Although it may be assumed that limbal and conjunctival damage implies a worse prognosis than isolated corneal damage, this has yet to be shown. In addition, a severe chemical injury involving the cornea but not the limbus, or vice versa, would be expected to be an uncommon event. We therefore propose to retain the degree of corneal damage (as proposed by Roper-Hall [3] and Ballen [4]) in grading of the injury (see Table 1).
Table 1 Modified Classification of Ocullar Chemical Injuries
Grade Cornea Limbal
IschaemiaConjunctival involvement Prognosis I Clear: epithelial damage only None None Good II Clear: epithelial damage only <1/3 <1/3 Good III+ Hazy cornea OR >1/3 OR >1/3 Guarded Thus grade I is identified by any isolated corneal epithelial injury. Grade II includes limbal or conjunctival involvement, but involving less than one third of the area involved. Grade III includes either a hazy cornea, defined as obscurity of the iris or pupil details (as per Roper-Hall’s and Ballen’s original descriptions), and/or greater than one third of limbal or conjunctival damage. With the advent of recent surgical techniques such as amniotic membrane transplants and limbal allografts, the prognosis of more severe ocular chemical injuries previously classified as Roper-Hall grade IV have improved and no longer carry a uniformly poor prognosis.[2] Therefore we reason that these cases can be included in Grade III of our proposed classification.
In conclusion, in the absence of good evidence for re-classifying ocular surface injuries, it would seem reasonable to keep to Roper-Hall / Ballen’s classification and to move it forwards by addressing the weaknesses of that system. We hope that the proposed grading system improves the consistency with which chemical injuries are reported in the literature, serves as a basis for controlled comparative evaluation of modern treatment options and stimulates further work in this area.
References
1. Kobayashi A, Shirao Y, Yoshita T, et al.Temporory amniotic membrane patching for acute chemical burns. Eye 2003; 17: 149-158
2. Dua HS, King AJ, Joseph A. A new classification of ocular surface burns. BJO 2001;85:1379-1383
3. Roper-Hall MJ. Themal and chemical burns. Trans Ophthalmol Soc UK 1965;85:631-53
4. Ballen PH, Hemstead NY.Treatment of chemical burns of the eye.Eye,Ear, Nose and Throat Monthly 1964;43:57-61
5. Wirtschafter JD., Ketcham JM, Weinstock RJ, et al. Mucocutaneous junction as the major source of replacement palpebral conjunctival epithelial cells. Inv Ophth Visual Science. 40(13):3138-46, 1999 Dec.
6. Wei ZG, Wu RL, Lavkar RM, et al. In vitro growth and differentiation of rabbit bulbar, fornix and palpebral conjunctival epithelia. Implications on conjunctival epithelial transdifferentiation and stem cells. Inv Ophth Visual Science 1993 Apr;34(5):1814-1828
7. Brodovsky SC, McCarty CA, Snibson G, et al. Management of alkali burns: an 11 year retrospective review. Ophthalmology. 2000;107(10):1829-1835
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Author's Reply
Submit responseDear Editor
We thank BV Kumar and S Prasad for their interest in our report describing the successful treatment of macular oedema (MO) secondary to branch retinal vein occlusion (BRVO) with intravitreal triamcinolone injection (IVTI).[1]
Although definitively establishing a clinical diagnosis of posterior vitreous detachment (PVD) may be problematic, our patient did not have a Weiss ring and no evidence of PVD in the macular region was visible on serial optical coherence tomography (OCT) scanning before or following treatment.
We believe it is unlikely that the primary mechanism of action of IVTI in treating MO is the induction of a PVD. We have treated another patient with OCT confirmed MO associated with BRVO which initially responded rapidly to IVTI with restoration of normal foveal contour and improvement in visual acuity. This patient subsequently developed recurrence of MO and visual loss one year following the initial treatment. Retreatment with IVTI resulted in a rapid improvement in visual acuity and restoration of foveal contour confirmed with OCT.
If induction of a PVD were the primary mechanism of IVTI efficacy in reducing MO, then repeated treatments with IVTI would not be expected to be efficacious as it would not be possible to induce a PVD more than once. This is at odds with our own frequent clinical experience of successful repeated IVTI’s for the treatment of recurrent MO associated with posterior uveitis or the reported efficacy of repetitive IVTI’s for MO associated with diabetic retinopathy [2] and pseudophakic cystoid MO.[3]
It might be interesting to speculate on the effect that the presence or absence of a pre-existing PVD may have on the efficacy of IVTA and we agree that it is important that such factors are considered in future reports.
References
(1) Prasad S, BV Kumar, S Prasad. How does intravitreal triamcinolone work? [electronic response to Chen et al. Intravitreal triamcinolone acetonide for ischaemic macular oedema caused by branch retinal vein occlusion] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/88/1/154#275
(2) Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920-7
(3) Conway MD, Canakis C, Livir-Rallatos C, et al. Intravitreal triamcinolone acetonide for refractory chronic pseudophakic cystoid macular edema. J Cataract Refract Surg 2003;29:27-33
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Ophthalmia neonatorum prophylaxis: Authors' reply
Submit responseDear Editor
We greatly appreciate the inquiry of Dr Vendantham and are happy to reply to his questions.[1]
While Dr Vendantham is correct regarding the definition of ophthalmia neonatorum including all infections acquired by an infant during the first 30 days of life, for the purposes of our study,[2] we were primarily interested in those cases resulting from neonatal exposure in the birth canal. This source of ophthalmia neonatorum is the one that would be influenced mainly by a second drop of Povidone-Iodine placed later on the day of birth. Infections postnatally that Dr Vendantham listed arising, while technically still within the definition of "ophthalmia neonatorum", would not be impacted by this second drop and therefore would not be directly affected by this study. Indeed, Dr Vendantham's interest in neonatal dacryocystitis would also fall within the same question since the reflux from the tear duct causing this infection generally does not arise until well after the first day of life.
The proportion of ophthalmia neonatorum cases acquired postnatally compared with those acquired during the birth process probably differs by country. The difference in predominant causative organisms (Staph aureus and enterococcus in the former situation as in India [3] vs. chlamydia and gonococcus in the latter) probably reflects the origin of the infection. Historically, in Kenya a high proportion of the infections probably arose from the birth process as reflected in the type of infecting organism. This, our Kenyan study was primarily directed toward those infections acquired during birth.
The fact that ophthalmia neonatorum in some countries seems to peak in certain seasons and not in other seasons should cause increased vigilance for this disorder in those countries. Our study, however, encompassed more than one full year of births in Kikuyu, Kenya. Therefore, the study included both the peaks and valleys of the incidence of ophthalmia neonatorum.
We thank Dr Vendantham for his interest and hope that in many countries, including India, ophthalmia neonatorum prophylaxis will either continue unabated or be initiated preferentially with the use of Povidone- Iodine.
Sincerely,
Sherwin J. Isenberg, M.D. Lantz Professor Pediatric Ophthalmology
Leonard Apt, M.D Professor of Ophthalmology Director Emeritus, Division of Pediatric Ophthalmology
References
(1) Vedantham V. Prophylaxis of ophthalmia neonatorum [electronic response to SJ Isenberg, L Apt, M Del Signore, S Gichuhi, NG Berman; A double application approach to ophthalmia neonatorum prophylaxis] ophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/87/12/1449#245
(2) Isenberg SJ, Apt L, Del Signore M, Gichuhi S,Berman NG. A double application approach to ophthalmia neonatorum prophylaxis. Br. J Ophthalmol 2003;87(12):1449-1452.
(3) Verma M, Chhatwal J. Vareghese PV. Neonatal conjunctivitis: a profile. Indian Pediatr 1994;31(11):1357-1361.
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Potential complications of phakic IOLs
Submit responseDear Editor
I read with interest the case report of Ashraff et al[1] where a posterior chamber phakic intraocular lens (PCPIOL) was used in a pseudophakic eye with axial myopia and pseudoexfoliation for the management of anisometropia. I would like to highlight a potential problem in such eyes: dislocation of PCPIOL into the vitreous cavity.
PCPIOLs are inserted blindly behind the iris and, depending on the design, allow their haptics to rest at the structures of the posterior chamber or float in it. Ultrasound biomicroscopy (UBM) identified haptic- zonules contact and lens rotation for the Implantable Contact Lens (ICL)[2] and the Phakic Refractive Lens (PRL),[3] although these PCPIOLs are intended to fixate at the ciliary sulcus and float in the posterior chamber respectively. Because of this potential haptic-zonules contact and lens rotation of PCPIOLs the entire zonular apparatus should be intact and healthy.
Pseudoexfoliation is characterised by progressive zonular disruption and axial myopia by zonular weakness and both conditions may lead to zonular defects. Although phakodonesis and iridodonesis may point towards zonular insufficiency, those signs may be absent in a number of eyes with occult zonular defects as shown in UBM studies.[4] Such zonular defects may result in spontaneous dislocation of the PCPIOL into the vitreous cavity. Two cases have been described already where PCPIOLs dislocated into the vitreous cavity through such defects. Kaya et al.[5] reported a case of dislocation of a silicone PCPIOL into the vitreous cavity following mild head injury three weeks postoperatively in a highly myopic eye (–19 DS). Another case of dislocation of a myopic PRL into the vitreous cavity has been reported by the European Clinical Trial with PRL group [Philipson B. PRL (phakic posterior chamber IOL)-the 12 month results of the European clinical trial. Presented at the XXI Congress of the ESCRS-Munich 2003]. I have recently reported a case of spontaneous dislocation of a PRL into the vitreous cavity in a young healthy female with high myopia two months postoperatively (spherical equivalent –19.5 D). (H Eleftheriadis, S Amoros, R Bilbao, MA Teijeiro. “Spontaneous dislocation of a Phakic Refractive Lens into the vitreous cavity”. Submitted for publication to the J Cataract Refract Surg December 2003).
The reported cases stress the importance of health and integrity of zonular apparatus in the long-term stability of PCPIOLs. Since pseudoexfoliation is a progressive disease that may lead to progressive zonular disruption and spontaneous IOL-bag dislocation into the vitreous cavity even many years after cataract surgery,[6] I think that PCPIOLs should not be used in pseudophakic eyes with pseudoexfoliation.
References
1. Ashraff NN, Kumar BV, Das A et al. Correction of pseudophakic anisometropia in a patient with pseudoexfoliation using an implantable contact lens. Br J Ophthalmol. 2004;88:309.
2. Trindade F, Pereira F, Cronemberger S. Ultrasound biomicroscopic imaging of posterior chamber phakic intraocular lens. J Refract Surg. 1998;14:497-503.
3. Garcia-Feijoo J, Hernandez-Matamoros JL, Mendez-Hernandez C et al. Ultrasound biomicroscopy of silicone posterior chamber phakic intraocular lens for myopia. J Cataract Refract Surg. 2003;29:1932-1939.
4. McWhae JA, Crichton AC, Rinke M. Ultrasound biomicroscopy for the assessment of zonules after ocular trauma. Ophthalmology. 2003;110:1340- 1343.
5. Kaya V, Kevser MA, Yilmaz OF. Phakic posterior chamber plate intraocular lenses for high myopia. J Refract Surg. 1999;15:580-585.
6. Jehan FS, Mamalis N, Crandall AS. Spontaneous late dislocation of intraocular lens within the capsular bag in pseudoexfoliation patients. Ophthalmology. 2001;108:1727-1731.
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How does intravitreal triamcinolone work?
Submit responseDear Editor
SDM Chen and colleagues present a case of successful treatment of macular oedema in the setting of ischaemic branch retinal vein occlusion (BRVO).[1]
Intravitreal triamcinolone is increasingly being used as part of our therapeutic armaterium in a wide range of conditions. However it’s mode of action is still to be fully elucidated. It is known that the induction of a posterior vitreous detachment (PVD) may have an important role in the resolution of macular oedema.[2] In patients undergoing an arterio-venous sheathotomy procedure for BRVO, surgical detachment of posterior hyaloid could be as important as the sheathotomy to improve macular oedema.[3]
In the reported case, it is possible that the intravitreal injection of triamcinolone may have induced a PVD and this may have contributed to the resolution of the macular oedema. Thus, it would be useful to know the status of the posterior hyaloid before and after triamcinolone injection in this case.
We feel that it is important that all relevant factors such as this are reported and discussed in this and similar reports in the literature. This will help us to evolve treatment alogarithms to target newer interventions such as intravitreal triamcinolone, to the patients most likely to benefit.
References
1. Chen SDM, Lochhead J, Patel CK, Frith P. Intravitreal triamcinolone acetonide for ischaemic macular oedema caused by branch retinal vein occlusion. Br J Ophthalmol 2004 Jan; 88: 154-5.
2. Yamaguchi Y, Otani T, Kishi S. Resolution of diabetic cystoid macular edema associated with spontaneous vitreofoveal separation. Am J Ophthalmol 2003 Jan; 135: 116-8.
3. Charbonnel J, Glacet-Bernard A, Korobelnik JF, et al. Management of branch retinal vein occlusion with vitrectomy and arteriovenous adventitial sheathotomy, the possible role of surgical posterior vitreous detachment. Graefes Arch Clin Exp Ophthalmol 2003 Dec 18 [Epub ahead of print].
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Reply to the author: Charles Bonnet Syndrome
Submit responseDear Editor
I thank Dr Tomsak for his reply[1] to my comments.[2]
In response to point one,we agree that historically CBS is a disorder described in the elderly, but as we mentioned in our previous reply, this can easily be explained by the higher incidence of visual loss in the elderly. Further, without formal child pyschiatry review it is difficult to give a incidence in the childhood of CBS. As you would expect the very young may not be able to differentiate between complex visual hallucinations described by most elderly patients as a very real phenomenon. Children may simply regard these are real visual stimuli and not hallucinations. The literature does not support the diagnosis of CBS on age alone. Secondly, we support the point that editorial constraints limited the paper somewhat. However, point three still seems to be a point of contention. In the abscence of Brimonidine drops, the diagnosis of CBS would have been justified. However, the onset and remission of CBS with starting and stopping of brimonidine drops leads to support the fact that these hallucinations are simply a pyscho-pharmakinetic response, as would be expected by any medication penetrating the blood-brain barrier. Indeed, as we described in our previous reply Brimonidine, and drugs of the same class, have been shown to cause neuropysciatric phenomenon similar to CBS, and that this effect described by the authours support this point of visual hallucinations as a side effect of brimonidine tartrate. We reiterate our point that these four patients suffered side effects and not CBS, as current literature does not support this view.
References
(1) Tomsak RL. Charles Bonnet Syndrome - Author reply [electronic response to RL Tomsak, CR Zaret, and D Weidenthal; Charles Bonnet syndrome precipitated by brimonidine tartrate eye drops] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/87/7/917#204
(2) Rahman I, Fernando BS, Harrison M. Charles Bonnet Syndrome and brimonidine: comments [electronic response to RL Tomsak, CR Zaret, and D Weidenthal; Charles Bonnet syndrome precipitated by brimonidine tartrate eye drops] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/87/7/917#189
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Author's reply
Submit responseDear Editor
I appreciate Dr Van Gelder’s thoughtful comments regarding the potential consequences of a UV+blue light absorbing intraocular lens (IOL) on circadian rhythmicity.[1] I agree that the clinical importance of retinal ganglion photoreceptors is currently unknown and that decreasing the amount of blue light reaching them might affect their function. Conversely, if photosensitive ganglia respond to circadian changes in their blue light exposure rather than just the magnitude of that exposure, a UV+blue light absorbing IOL may not impair ganglion function.
Dr Van Gelder re-emphasizes our finding that IOL chromophore selection balances the potential loss of useful visual function against a reduction in the risk of acute UV-blue phototoxicity. Our paper did not state, however, that UV+blue absorbing IOLs were desirable for people with outer retinal degeneration. Indeed, blue light is more important in scotopic than photopic vision. Individuals with age-related macular degeneration have greater nighttime visual problems than their peers without it, and these scotopic problems may be exacerbated if a significant amount of blue light is blocked by an IOL.
Reference
(1) Van Gelder RN. Blue light and the circadian clock [electronic response to Mainster MA and Sparrow JR; How much blue light should an IOL transmit?] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/87/12/1523#257
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Blue light and the circadian clock
Submit responseDear Editor
Drs Mainster and Sparrow have provided an excellent perspective on the relative merits and difficulties of extending IOL absorption into the blue portion of the spectrum.[1]
However, they have not considered an unintentional consequence of blockage of the blue portion of the spectrum: reducing the activity of intrinsically photosensitive retinal ganglion cells.[2, 3] These cells subserve several non-visual ocular photoreceptive tasks, most prominently the entrainment of the circadian clock to external light-dark cycles.[4] Pupillary light responses in mice are also at least partially controlled by this system, which appears to use a novel opsin (melanopsin) [5,6] and possibly also a flavoprotein (cryptochrome) [7,8] as photopigments.
Experiments in mice have suggested that the action spectrum for these photopigments peak in the blue, at approximately 480 nm, but with substantial sensitivity to blue light to 430 nm.[9] This system appears to be functional in humans as documented by the action spectrum for light suppression of the pineal hormone, melatonin.[10,11]
The clinical importance of these photoreceptors is presently unknown, although it appears that loss of retinal ganglion cells predisposes children and young adults to disorders of sleep timing that outer retinal disease does not.[12] While, as the authors note, there may be substantial benefit in blocking blue-light phototoxicity, particularly for patients with pre-existing outer retinal degeneration, these IOLS lenses may have unintended consequences with respect to the timing of sleep and wakefulness or levels of certain neuro-hormones.
References
1. Mainster MA, Sparrow JR. How much blue light should an IOL transmit? Br. J. Ophthalmol. 2003;87:1523-9.
2. Berson DM. Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci. 2003;26:314-20.
3. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295:1070-3.
4. Freedman MS, Lucas RJ, Soni B, et al. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors Science. 1999;284:502-4.
5. Panda S, Provencio I, Tu DC, et al. Melanopsin is required for non -image-forming photic responses in blind mice. Science. 2003;301:525-7.
6. Hattar S, Lucas RJ, Mrosovsky N, et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature. 2003;424:75-81.
7. Van Gelder RN, Wee R, Lee JA, Tu DC. Reduced pupillary light responses in mice lacking cryptochromes. Science. 2003;299:222.
8. Selby CP, Thompson C, Schmitz TM, Van Gelder RN, Sancar A. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc. Natl. Acad. Sci. U. S. A. 2000;97:14697-702.
9. Lucas RJ, Douglas RH, Foster RG. Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat. Neurosci. 2001;4:621-6.
10. Brainard GC, Hanifin JP, Greeson JM, et al. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J. Neurosci. 2001;21:6405-12.
11. Thapan K, Arendt J, Skene DJ. An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J. Physiol. (Lond). 2001;535:261-7.
12. Wee R, Van Gelder RN. Sleep disturbances in young subjects with visual dysfunction. Ophthalmology. In press.
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