Dear Editor

The authors of this article (Tan J C H, and Hitchings R. Non-penetrating glaucoma surgery: the state of play. Br J Ophthalmol 2001;85:234-237) should be commended on attempting to tackle this issue. Nevertheless we do feel that their fundamental points and principal arguments merit reconsideration.

The authors state categorically that "long term outcomes do not exit for the newer non-penetrating surgery technique" when in fact long term (43.2 months +/- 14.3 (SD)) results for deep sclerectomy with collagen implant have been presented to the European Glaucoma Society (EGS) Glaucoma Symposium, 2000, and have also been published some time ago.[1] The study provided a qualified success rate of 94.8% and the complete success rate, 61.9% after 60 months (survival analysis), with a mean IOP at end of follow-up of 11.8 +/- 3. The study reported no surgically induced cataract of the whole series of 105 patients.

The authors, unfortunately, failed to cite a landmark study[2] comparing deep sclerectomy without an implant to trabeculectomy in the two eyes of the same patient in a prospective randomised fashion. At 12 months, mean IOP reduction was 12.3 +/- 4.2 (sclerectomy) versus 14.1 +/- 6.4 mmHg (trabeculectomy) (P = 0.15), and an IOP Furthermore the authors cite a study by Gandolfi as personal communication supposedly providing evidence that "trabeculectomy produces lower and better sustained IOP control than either viscocanalostomy or deep sclerectomy". The authors fail to mention however, that in this particular study postoperative YAG goniopunctures were considered as a failure criteria. Excluding goniopuncture from the success criteria would easily be compared to considering laser suture lysis or even YAG capsulotomies to be failure criteria of glaucoma or cataract surgeries. Furthermore Gandolfi concluded that Deep sclerectomy was associated with lower perturbation of lens nuclear transparency (personal communication, January 2002).

In another point worthy of reconsideration the authors site a study [3] that allegedly draws attention to high rates of hypotony and hyphaema after intraoperative conversion of deep sclerectomy to trabeculectomy following accidental intraopeartive perforation of the trabeculo- Descemet's membrane (TDM). However the authors again fail to mention, when quoting this specific study, that "when deep sclerectomy is complicated with a perforation of the TDM, the long term success rate of the surgery is similar to that of trabeculectomy". This conclusion would encourage the surgeons to start their surgery as a deep sclerectomy, knowing that in case of a perforation and a subsequent transformation to trabeculectomy, the chances of success would be similar to initial trabeculectomy.

The authors of the paper at hand compare in their figures viscocanalostomy, deep scelerectomy without an implant, deep sclerectomy with collagen implant, and deep sclerectomy without suturing the superficial flap to each other, and thus drawing certain conclusions. The different techniques have one thing in common, the element of non- perforation. It is not useful to compare apples and pears.

A major factor in the conflicting, often contradictory, results available is the element of long learning curves. As an example one group reported 0% success rate in their first series of viscocanalostomy patients [4] and then presented their second series with a success rate of 15%.[5]

The same group also analyzed the depth of their dissection of the deep sclera [6] to find that they dissected too superficially in 48% of their cases and too deeply in 17%. Meaning that the proper depth of dissection, which should bisect transversally the Schlemm's canal deroofing it, was not achieved in the majority of their cases.

To achieve successful non-penetrating surgery, the dissection of the deep sclerectomy needs to be correct. This entails a total excision of corneal stroma behind Descemet's membrane and the excision of the inner wall of Schlemm's canal and the juxtacanalicular trabeculum. An implant has to be used to maintain the scleral space patent.[7] Laser goniopuncture should be performed at any postoperative stage when IOP mounts beyond the target pressure. We do however wholeheartedly agree with the authors on the importance of conducting a large-scale multinational randomised prospective trial as the only possible method to compare non-penetrating glaucoma surgery, or any other new surgical practice, to trabeculectomy.

Tarek Shaarawy¹, MD and André Mermoud², MD

1. Head Glaucoma unit, Memorial Research Institute of Ophthalmology, Giza, Egypt.
2. Head Glaucoma unit, University of Lausanne, Switzerland.

References

(1) Shaarawy T, Karlen M, Schnyder C, Achache F, Sanchez E, Mermoud A. Five-year results of deep sclerectomy with collagen implant. J Cataract Refract Surg 2001;27:1770-8.

(2) El Sayyad F, Helal M, El Kholify H, Khalil M, El Maghraby A. Nonpenetrating deep sclerectomy versus trabeculectomy in bilateral primary open-angle glaucoma. Ophthalmology 2000;107:1671-4.

(3) Sanchez E, Schnyder CC, Mermoud A. [Comparative results of deep sclerectomy transformed to trabeculectomy and classical trabeculectomy]. Klin Monatsbl Augenheilkd 1997;210:261-4.

(4) Jonescu-Cuypers C, Jacobi P, Konen W, Krieglstein G. Primary viscocanalostomy versus trabeculectomy in white patients with open-angle glaucoma: A randomized clinical trial. Ophthalmology 2001;108:254-8.

(5) Dietlein, T. S. and Krieglstein, G. K. Morphology and pressure- reducing efficacy after viscocanalostomy. 23. 2001. Paris, European Glaucoma Society. Closed Meeting of the European Glaucoma Society.

(6) Dietlein TS, Luke C, Jacobi PC, Konen W, Krieglstein GK. Variability of dissection depth in deep sclerectomy: morphological analysis of the deep scleral flap. Graefes Arch Clin Exp Ophthalmol 2000;238:405-9.

(7) Shaarawy, T., Nguyen Chr, Schnyder, C., Achache, F., and Mermoud, A. Comparative study between deep sclerectomy with and without collagen implant: Long term follow-up. Invest Ophthalmol42(4), S544. 2001.

Dear Editor

Saito et al. present a patient with Terson’s syndrome and vitreous hemorrhage who underwent pars plana vitrectomy and was noted postoperatively to have developed an ophthalmic artery occlusion. They propose that the ophthalmic artery was occluded by the spontaneous release of an embolus from an atheromatous plaque in the internal carotid artery. This seems unlikely in a 39-year-old male without a prior history of symptomatic atherosclerotic disease. Although the authors identified plaques in the patient’s carotid artery by ultrasound, these can be seen in 11% of asymptomatic males under age 40 and may therefore be an incidental finding in this case.[1]

An alternate explanation for the patient’s ocular findings is trauma from the retrobulbar injection. Intravascular injection into the ophthalmic artery has been reported as a complication of retrobulbar anesthesia.[2] It is possible that either an intravascular injection or simply needle-tip trauma resulted in thrombus formation with obstruction of flow in the ophthalmic artery. It should also be noted that although acute ophthalmic artery occlusion is the presumed diagnosis, the same findings could result from simultaneous obstructions of the retinal and choroidal circulations,[3] also a potential consequence of errant retrobulbar injection. The possibility that the patient’s chorioretinal disturbance could have been iatrogenic highlights the importance of a thorough preoperative discussion with patients about the risks and benefits of different methods of delivering anesthesia for ophthalmic surgery.

References

(1) Sun Y, Lin CH, Lu CJ, et al. Carotid atherosclerosis, intima media thickness and risk factors—an analysis of 1781 asymptomatic subjects in Taiwan. Atherosclerosis 2002;164:89-94.

(2) Morgan CM, Schatz H, Vine AK, et al. Ocular complications associated with retrobulbar injections. Ophthalmology 1988;95:660-665.

(3) Brown GC, Magargal LE, Sergott R. Acute obstruction of the retinal and choroidal circulations. Ophthalmology 1986;93:1373-1382.

Dear Editor

We were interested to read the letter by Patel et al. reporting the unusual and striking fundus appearance of retinal arteriolar calcification in association with chronic renal failure.[1] However, we feel that two important conditions have been omitted from the comment, which merit further discussion.

First, Monckeberg’s sclerosis, which in its classic form is characterised by ‘pipe-stem’ calcific deposition in the medial coat of muscular arteries in middle-aged and elderly individuals,[2] and is described with widespread systemic distribution.[3,4] Interestingly though, a juvenile form is seen, particularly in association with chronic renal failure and diabetes.[5] The pathological mechanism of Monckeberg’s sclerosis is uncertain, but is thought to encompass elements both of dystrophic and metastatic calcification.[6] In the reported case, it would be of interest to know if there was any evidence of vascular calcification elsewhere in this individual, or whether it was localised to the retinal arterioles only.

Secondly, Senior-Loken syndrome (renal-retinal syndrome, nephronophthisis associated with retinitis pigmentosa or retinal aplasia) is also germane to this discussion.[7] Nephronophthisis is a major cause of progressive medullary cystic renal disease leading to chronic renal failure in adolescents.[8] It is associated with a variable retinal phenotype, a reflection of both clinical and genetic heterogeneity. When associated with retinitis pigmentosa, there is an absence of the classic bone spicule pigmentation, but optic nerve head pallor and attenuation of the blood vessels is seen. Also, electroretinographic alterations have been reported in nephronophthisis despite normal a normal fundus examination.[9] In view of the phenotypic overlap seen with the reported case, results of electroretinography would be pertinent to the discussion. We would also advocate a molecular genetic analysis at the known loci associated with Senior-Loken syndrome, which could potentially reveal an interesting new allelic variant.

Finally, whilst the fundus photograph elegantly demonstrates the stark changes seen in the retinal vasculature, this evidence could be further augmented with the addition of an ultrasound B-scan image demonstrating the pathognomonic echogenic features of intra-ocular calcification.

Moin Mohamed
Vision Research Group
Molecular Medicine Unit
University of Leeds

Martin McKibbin
Eye Clinic
St James’s University Hospital
Beckett Street
Leeds

References

(1) Patel DV, Snead MP, and Satchi K. Retinal arteriolar calcification in a patient with chronic renal failure. Br J Ophthalmol 2002;86:1063

(2) Juergens JL et al. Peripheral vascular diseases. 5th edition. Philadelphia: W Saunders. 1980. pp.238-240.

(3) Lachman AS, Spray TL, Kerwin DM, Shugoll GI, Roberts WC. Medial calcinosis of Monckeberg. A review of the problem and a description of a patient with involvement of peripheral, visceral and coronary arteries. Am J Med 1977 Oct;63(4):615-22.

(3) Castillo BV Jr, Torczynski E, Edward DP. Monckeberg's sclerosis in temporal artery biopsy specimens. Br J Ophthalmol 1999 Sep;83(9):1091-2.

(4) Monckeberg's sclerosis: an unusual presentation. Top C, Cankir Z, Silit E, Yildirim S, Danaci M. Angiology 2002 Jul-Aug;53(4):483-6.

(5) Byts' IuV, Holdobina OV, Dosenko VIe, Dudko MO, Larionova NA. The current concepts of the pathogenesis of Monckeberg-type arteriosclerosis. Fiziol Zh 2000;46(2):64-72.

(6) Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: #266900: 6/10/2002. http://www.ncbi.nlm.nih.gov/omim/

(7) Gusmano R, Ghiggeri GM, Caridi G. Nephronophthisis-medullary cystic disease: clinical and genetic aspects. J Nephrol 1998 Sep-Oct;11(5):224-8.

(8) Orssaud C, Kleinknecht C, Habib R, Broyer M. Hereditary chorioretinal degeneration and nephronophthisis. The role of Senior-Loken syndrome. Ophtalmologie 1989 Sep-Dec;3(4):270-2.

Dear Editor

We read with interest the remarks of Crowston et al. [1] on our article entitled "Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique".[2] We showed that the TUNEL technique revealed a far higher percentage of endothelial cells (ECs) irreversibly engaged in a cell death process than that obtained by trypan blue staining.

The two techniques were performed sequentially: after observation of trypan blue staining, corneas were immediately fixed in formaldehyde for TUNEL. Crowston et al. suggest that the trypan blue itself and/or the time spent outside the organ-culture medium before fixing in formaldehyde may have caused an artefactual increase in the percentage of TUNEL-positive ECs. Two arguments counter this remark:
1. The trypan blue staining procedure is identical to that used in all European cornea banks that use organ culture during endothelial examination(s) of grafts. Neither the low concentration of trypan blue (0.4%) nor the short exposure time (about 1 minute) nor the short incubation in the presence of 0.9% NaCl has ever been incriminated in ECs over-mortality in routine practice.[3] Moreover, the innocuity of injections of trypan blue into the anterior chamber, a common feature during cataract surgery, has been well demonstrated.[4]

2. The time spent outside the organ-culture medium before fixing in formaldehyde, a period required for vital staining and microscopic examination of the endothelium, lasts only a few minutes. The cornea remains under the microscope for about one minute only, the time needed for image acquisition. Such rapidity is possible by using a prototype automatic analyser of the endothelium, which we developed and have recently published.[5] This is very probably insufficient time for DNA fragmentation to occur in the proportion we observed. Moreover, the fixing of the endothelial layer in 10% formaldehyde is immediate, and prevents any continuation of fragmentation phenomena. On balance, it is highly unlikely that the succession of markings is responsible for the discrepancy between the positivity percentages of the two techniques. In addition, we chose not to perform the two techniques simultaneously on paired corneas or on the halves of one cornea because we wanted to superimpose the two stains on the same cornea and thus obtain a double cell staining.

The second remark by Crowston et al. is particularly interesting. We too were surprised by the high percentage of TUNEL-positive ECs (mean 12.7%, SD 16.4). This may imply that all the cells died within 8 days, which was evidently not the case. We believe this apparent contradiction can be explained by the following theory. The TUNEL staining is positive during a relatively long window (24-48 hours [6]). The TUNEL index, measured at a given moment, provides a global view of all the cells with fragmented DNA. However, the DNA fragmentation may be at different stages, and the cells very likely spread according to a Gaussian distribution. Therefore the cells, which are TUNEL-positive at a given moment, will not all die instantaneously and simultaneously. Only the cells furthest to the right on the curve will die in the very short term, and it is probably these that are liable to be revealed by trypan blue. If it were possible to perform TUNEL on two consecutive days, the percentage of positive cells revealed would probably be very similar, but a large majority of the positive cells recorded on the second day would have already been counted on day one... It is, however, undeniable that the cells TUNEL-positive at a given moment will all die eventually. In other words, we believe that, at the end of storage, corneas contain a number of ECs engaged in an irreversible cell-death process far more extensive than the highly unreliable trypan blue staining technique suggests.

References

(1) Crowston JG, Healey PR, Maloof A, et al . Quantifying corneal endothelial cell death. Br J Ophthalmol 2002;86:1068.

(2) Gain P, Thuret G, Chiquet C, et al . Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique. Br J Ophthalmol 2002;86:306-10.

(3) Sperling S. Evaluation of the endothelium of human donor corneas by induced dilation of intercellular spaces and trypan blue. Graefes Arch Clin Exp Ophthalmol 1986;224:428-34.

(4) Norn MS. Per operative trypan blue vital staining of corneal endothelium. Eight years' follow up. Acta Ophthalmol 1980;58:550-5.

(5) Gain P, Thuret G, Kodjikian L, et al. Automated tri-image analysis of stored corneal endothelium. Br J Ophthalmol 2002;86:801-8.

(6) Mesner PW, Epting CL, Hegarty JL, et al. A timetable of events during programmed cell death induced by trophic factor withdrawal from neuronal PC12 cells. J Neurosci 1995;15:7357-66.