Maninder Bhogal

Descemet Stripping Automated Endothelial Keratoplasty After Failed Penetrating Keratoplasty: Survival, Rejection Risk, and Visual Outcome

IMPORTANCE Descemet stripping automated endothelial keratoplasty (DSAEK) for isolated endothelial dysfunction has become the preferred surgical option for many corneal surgeons. However, there are limited large-scale reports on DSAEK survival and clinical variables affecting the risk of rejection and failure after failed penetrating keratoplasty (PK). OBJECTIVE To report the survival, risk factors for graft rejection and failure, and visual outcome of DSAEK after failed PK. DESIGN, SETTING, AND PARTICIPANTS A multicenter retrospective interventional case series included patients recruited from 6 tertiary referral surgical centers: 3 in the United States, 2 in Europe, and 1 in Asia. A total of 246 consecutive eyes (246 patients) that underwent DSAEK after failed PK, with a minimum follow-up period of 1 month, was included. Data comprising demographic details, preoperative and postoperative risk factors, time to rejection, time to failure, and corrected distance visual acuity were collected. MAIN OUTCOMES AND MEASURES Cumulative probability of graft survival, hazard ratio estimates for survival, and corrected distance visual acuity were determined. RESULTS The mean (SD) recipient age was 63.2 (16.6) years and the median follow-up period was 17 months (interquartile range, 6-30 months). One-third of the grafts (n = 82) had follow-up data for more than 2 years; 18.3% had more than 1 failed PK before DSAEK. In total, 19.1% (47 of 246) of DSAEK grafts failed. The cumulative probability of DSAEK survival after a failed PK was 0.89 (95% CI, 0.84-0.92), 0.74 (95% CI, 0.64-0.81), and 0.47 (95% CI, 0.29-0.61) at 1 year, 3 years, and 5 years, respectively. Based on multivariate analysis, significant preoperative risk factors for failure were young recipient age (hazard ratio [HR], 5.18 [95% CI, 1.57-17.18]), previous tube filtration surgery (HR, 5.23 [95% CI, 1.47-7.33]), and rejection episodes before PK failure (HR, 3.28 [95% CI, 1.47-7.33]); single-surgeon centers had a protective effect. Any rejection episode prior to PK failure was a significant predictor of post-DSAEK rejection, which in turn was a significant predictor of DSAEK failure. After a median follow-up of 17 months, 33.3% of the grafts achieved 0.3 or greater logMAR (20/40) corrected distance visual acuity. CONCLUSIONS AND RELEVANCE Descemet stripping automated endothelial keratoplasty after failed PK combines greater wound stability and reduced suture-related complications, with visual outcomes and graft survival rates comparable to those of a second PK.

Anterior segment slitlamp photography using the iPhone.

(17.9%, 7/39) or incision (5.1%, 2/39). Most respondents reported no serious ocular hemorrhagic events from continuing antithrombotic agents (92.3%, 36/39) or serious thrombotic events from discontinuing them (94.4%, 34/36). Most (75.0%, 30/40) reported a greater concern about a perioperative thromboembolic event from discontinuing antithrombotic agents than about a perioperative ocular hemorrhage from continuing them. These results indicate that in most VHA hospitals, oral antithrombotic agents are not discontinued prior to cataract surgery. This finding is similar to the finding in a recent report from the Canadian Society of Cataract and Refractive Surgery 2 that most members (74.4%) did not discontinue antithrombotic therapy before cataract surgery. The rationale for this practice pattern appears to be a greater concern about the systemic risks of discontinuing antithrombotic agents than the risks of perioperative hemorrhagic ocular complications from continuing them. This rationale is supported by reports that ocular hemorrhages in cataract surgery patients on antithrombotic agents generally do not affect visual outcomes. 4,5,6 The weaknesses of a survey-based study have been described 3 and include limitations in generalizability due to distinct setting (most respondents worked in teaching hospitals rather than ambulatory surgery centers) and patient population (U.S. veterans) and potential bias due to a response rate of 45%. This study provides more insight into how cataract surgeons in the VHA currently manage patients on antithrombotic agents. Further research is needed to determine whether differences in management of antithrombotic therapy during cataract surgery are associated with distinct patient outcomes.

Cataract surgery outcome in eyes with keratoconus

Background To review the refractive outcome of cataract surgery in eyes with keratoconus. Methods We retrospectively reviewed the medical records of 64 consecutive patients (92 eyes) who underwent cataract surgery with implantation of a spherical intraocular lens (IOL). We recorded the method of refractive correction and the effect of the keratometry (K) on the biometry prediction error (BPE). Results 35 eyes had mild keratoconus (mean K<48 dioptres (D)), 40 had moderate keratoconus (mean K 48 D to 55 D) and 17 had severe keratoconus (mean K>55 D). Actual K values were used in all eyes with mild or moderate keratoconus with a target refraction of approximately −1.0 D in mild keratoconus and −1.5 D in moderate keratoconus that resulted in a mean BPE of 0.0 D and +0.3 D, respectively. The actual K values were used in eight of the 17 eyes with severe keratoconus with a mean target refraction of −5.4 D, which resulted in a mean BPE of +6.8 D. In the remaining nine eyes, a standard K value of 43.25 D was used with a mean target refraction of −1.8 D, which resulted in a mean BPE of +0.6 D. Conclusions Using the actual K values with a target of low myopia is a suitable option for spherical IOL selection for eyes with a mean K of ≤55 D. When there is severe keratoconus, the use of actual K values can result in a large hyperopic error and the use of standard K value in these eyes should be considered.

Graft profile and thickness as a function of cut transition speed in Descemet-stripping automated endothelial keratoplasty

PURPOSE: To determine the profile of endothelial keratoplasty lenticules prepared using a microkeratome and evaluate the impact of varying cut transition speed on cut depth and profile using anterior segment optical coherence tomography (AS‐OCT). SETTING: Department of Cornea and External Diseases, Moorfields Eye Hospital, London. United Kingdom. DESIGN: Experimental study. METHODS: Fourier‐domain AS‐OCT was used to image 25 corneal specimens before and after microkeratome dissection with a 350 μm head. A pilot series of 7 corneas were cut and imaged with the following 18 corneas divided into regular cut transition speed and slow cut transition speed groups (9 in each). Proximal, central, and distal precut corneal thickness and post‐cut residual bed thickness were measured using the integrated caliper tools of the Fourier‐domain AS‐OCT device. Cut depth was calculated by subtraction. RESULTS: The slower microkeratome pass speed produced significantly thinner donor lenticules (mean 148 ± 45 μm [SD]) than the standard pass speed (mean 234 ± 35 μm) (P≤.0001). In both groups, significant asymmetry was observed in donor lenticules with a deeper cut depth and a thinner lenticule at the beginning of the microkeratome pass (proximal stromal bed). The mean difference between the proximal and distal stromal bed thickness was 61 ± 63 μm in the standard group and 52 ± 22 μm in the slow‐pass group (P=.159). CONCLUSIONS: Reducing the transition speed in microkeratome dissection produced thinner donor lenticules. Thickness asymmetry is an inherent flaw with current microkeratome dissection that cannot be easily corrected by altering preparation technique. Financial Disclosure: Neither author has a financial or proprietary interest in any material or method mentioned.

Organ culture storage of pre-prepared corneal donor material for Descemet's membrane endothelial keratoplasty

Purpose To evaluate the effect of media composition and storage method on pre-prepared Descemets membrane endothelial keratoplasty (DMEK) grafts. Methods 50 corneas were used. Endothelial wound healing and proliferation in different media were assessed using a standard injury model. DMEK grafts were stored using three methods: peeling with free scroll storage; partial peeling with storage on the stroma and fluid bubble separation with storage on the stroma. Endothelial cell (EC) phenotype and the extent of endothelial overgrowth were examined. Global cell viability was assessed for storage methods that maintained a normal cell phenotype. Results 1 mm wounds healed within 4 days. Enhanced media did not increase EC proliferation but may have increased EC migration into the wounded area. Grafts that had been trephined showed evidence of EC overgrowth, whereas preservation of a physical barrier in the bubble group prevented this. In grafts stored in enhanced media or reapposed to the stroma after trephination, endothelial migration occurred sooner and cells underwent endothelial-mesenchymal transformation. Ongoing cell loss, with new patterns of cell death, was observed after returning grafts to storage. Grafts stored as free scrolls retained more viable ECs than grafts prepared with the fluid bubble method (74.2± 3% vs 60.3±6%, p=0.04 (n=8). Conclusion Free scroll storage is superior to liquid bubble and partial peeling techniques. Free scrolls only showed overgrowth of ECs after 4 days in organ culture, indicating a viable time window for the clinical use of pre-prepared DMEK donor material using this method. Methods for tissue preparation and storage media developed for whole corneas should not be used in pre-prepared DMEK grafts without prior evaluation.

Global cell-by-cell evaluation of endothelial viability after two methods of graft preparation in Descemet membrane endothelial keratoplasty

Purpose To describe a novel method of global cell viability assessment for Descemet membrane endothelial keratoplasty (DMEK) and the comparison of two contemporary methods of donor tissue preparation. Methods DMEK transplants were prepared using two different methods: liquid bubble separation and manual peeling (n=8 each group). Samples were incubated with Hoechst, calcein-AM and ethidium homodimer prior to mounting on a curved imaging chamber. Z-stacked fluorescence microscopy images were combined to produce an in-focus global image capable of resolving all cell nuclei. Image processing software was used to define a calcein-positive live cell area, count all cell nuclei within this area and subtract ethidium-positive dead cells to derive the total viable endothelial cell count. Corrected global cell density was calculated by dividing the number of viable cells by the graft area, which had been corrected for imaging a curved surface. Results Corrected global cell density was lower than the central endothelial cell density in both groups: 85.5% of the pre-preparation central endothelial cell density in the peel group and 75.8% in the bubble group. Corrected global cell density was significantly lower in the liquid bubble separation group than in the peel group (p=0.04). Conclusions Eye bank estimations of central endothelial cell density overestimate true cell density after graft preparation in DMEK. A peel method is less damaging and more consistent than a liquid bubble method. Cell loss correlated strongly with the degree of stromal hydration prior to bubble separation in the liquid bubble group.

Use of a single peripheral triangular mark to ensure correct graft orientation in Descemet membrane endothelial keratoplasty.

rine have been reported over the past 6 decades. Fraunfelder and Scafidi reviewed the complications after topical phenylephrine. Fifteen of 32 entailed cardiac arrest, and 11 of those were fatal. Others have pointed out the occurrence of severe pulmonary hypertension, systemic hypertension, and rupture of intracranial aneurysms. Perhaps only a small subset of patients is at risk. Preexisting cardiac arrhythmiamaypredispose to induction of ventricular fibrillation. The patient’s cardiovascular status and history must be known before deciding to use phenylephrine in or on the eye. Cataract surgeons around the world use various concentrations of intracameral phenylephrine, some much lower concentrations than the concentration we used in our patient. This may be safer relative to the total dose of phenylephrine exposure; however, the efficacy of the various concentrations is not clear. In 2003, Lundberg and Behndig compared pupil dilation using intracameral phenylephrine (15 mg/mL) alone with dilation using topical mydriatics (cyclopentolate 1.0% and phenylephrine 10.0%). They found that the intracameral mydriatic alone produced a significant pupil dilation of 6.7 mm G 1.0 (SD), which was sustained throughout the procedure. However, this dilation was statistically less than the dilation with topical mydriatics, which was 7.7 G 1.0 mm but had shorter sustainability. In 2010, the same group showed that phenylephrine given intracamerally resulted in the same mydriatic effect in concentrations between 0.15 mg/mL and 5.00 mg/mL but had a significantly greater effect in higher concentrations of 15 mg/mL and 30 mg/mL. Topical mydriatics have lower bioavailability and higher systemic absorption. In patients with cardiovascular risk factors, it may be plausible to use only intracameral phenylephrine for dilation or topical cyclopentolate 1.0% and intracameral phenylephrine, reducing the systemic absorption and side effects of the drug. Whether this would be effective in reducing the risk for IFIS in patients on a antagonists is unknown as no studies have performed a direct comparison. Prudence dictates that one consider the total dose of phenylephrine used, preferring 2.5% drops to 10.0%. Bilateral application doubles the dose. Surgeons might prefer to use iris hooks or a Malyugin ring rather than extra phenylephrine. We recommend cardiovascular monitoring of patients with risk factors and the ready availability of anesthetists experienced in cardiopulmonary resuscitation. Intermittent verbal communicationwith thepatient and use of topical anesthesia (enabling the surgeon to see whether the patient loses voluntary fixation) can aid immediate recognition of the onset of ventricular fibrillation. This caution applies to pupil dilation for both cataract surgery and photography.

Stability of Eyelid Height After Graded Anterior-Approach Lid Lowering for Dysthyroid Upper Lid Retraction

Objective: To investigate the outcome of a modified anterior approach surgical procedure for the correction of primary upper eyelid retraction in thyroid eye disease. Methods: A retrospective review of 52 consecutive cases (in 32 patients) of anterior-approach graded upper lid lowering for the treatment of primary eyelid retraction, carried out at Moorfields Eye Hospital between 2006–2009 was conducted. Measurements of upper margin-reflex distance (MRD), upper lid skin crease height and skin fold height were taken from clinical records and photographs. A comparison between pre-operative and both early and late post-operative measurements was conducted, with a maximal follow-up of 12 months. Surgery was considered successful when all of the following criteria were met; an upper lid margin covering 0.5–1.5 mm of the superior cornea in the 12 o’clock position, smooth eyelid contour, skin crease height within 6–10 mm or upper lid skin fold within 2–5 mm of the lid margin, symmetry of lid position (difference in MRD of <1 mm between both eyes) and patient satisfaction. Results: A successful outcome was achieved in 86.5% (45/52) of lids with a single procedure. For the whole group, the mean MRD was 7.0 mm pre-operatively and 3.6 mm at 1 month after surgery. The corresponding values from photographic estimates were 6.5 mm and 3.6 mm, respectively. These values remained stable over the maximum follow-up period of 12 months. Under-correction occurred in 6/52 (11.5%) lids, one of which had persistent lateral flare, whereas over-correction occurred in 1/52 (2%). Conclusions: The described surgical approach produces reasonably predictable and stable outcome for upper eyelid lowering in patients with thyroid eye disease.

Allogeneic Descemet's Membrane Transplantation Enhances Corneal Endothelial Monolayer Formation and Restores Functional Integrity Following Descemet's Stripping

Purpose To characterize the differences in corneal endothelial wound healing in the presence or absence of Descemets membrane (DM), in vivo. Methods New-Zealand white rabbits were subjected to 7-mm endothelial wound either by scraping (n = 8; DM intact), peeling (n = 6; DM removed), or a combinatory scrape/peel wound (n = 6). In a second experiment, rabbits underwent peel wound with immediate transplantation of pure decellularized human DM (n = 4). In vivo endothelial migration was assessed via trypan blue staining. Recovery of corneal clarity and thickness was performed by using slit-lamp biomicroscopy and optical coherence tomography. Cell proliferation, phenotype, and morphology were assessed by using immunofluorescence and scanning electron microscopy. Results In vivo wound closure was faster in the presence of DM; 25.4% ± 1.4%/d versus 5.5% ± 0.6%/d (P < 0.0001). At day 8, complete wound closure was seen in all of the scrape samples but none of the peel group, with wound closure preceding clinical recovery by approximately 6 days in the scrape group. Endothelial cells in the scraped areas reformed functional monolayers capable of restoring corneal thickness and transparency whilst those in the peeled area underwent mesenchymal-like transformation resulting in scar formation. Transplanting decellularized DM in animals receiving a peel wound resulted in clarity and thickness comparable to the scrape group. Endothelial proliferation (Ki67 +ve cells) was higher in scraped versus peeled areas: 54.7% ± 3.5% vs. 8.8% ± 0.7%, (P < 0.01). Conclusions The presence of DM promoted endothelial wound healing, proliferation, and maintenance of a normal phenotype. DM transplantation recovered the abnormal peel phenotype back to that observed after endothelial scraping.

Sight-threatening intraocular pressure due to an upper arm dialysis fistula

www.thelancet.com Vol 386 July 4, 2015 101 In October, 2013, a 52-year-old man presented with 1 month of left eye redness, intermittent blurred vision, and occasional diplopia. He had quiescent treated bilateral proliferative diabetic retinopathy, controlled hypertension, and dialysis-dependent diabetic nephropathy. 1 month before his left forearm arterio venous dialysis fi stula had failed and he had had surgical formation of an upper arm (brachiobasilic) fi stula. On examination, visual acuity was unchanged from previous testing (6/9·5 bilaterally) but colour vision was reduced on the right. Goldmann visual fi elds and extraocular movements were normal. The left eye had tortuous, dilated conjunctival vessels and mild proptosis (fi gure). Intraocular pressure on the left was raised to a sight-threatening level (40 mm Hg) but was normal on the right (16 mm Hg). Fundoscopy showed retinal haemorrhages bilaterally and right optic disc swelling. These features suggested a carotid cavernous fi stula and CT angiography showed prominence of both ophthalmic veins and the left inferior petrosal sinus, but cerebral angiography showed no carotid cavernous fi stula. We therefore did angiography via the left subclavian artery (video), which showed complete occlusion of the left brachiocephalic vein with high pressure venous return from the fi stula travelling up the left jugular veins, with retrograde fl ow in the left inferior petrosal sinus, the cavernous sinus, and both superior ophthalmic veins. We confi rmed that the brachiobasilic fi stula was the cause of the abnormal ocular signs by occluding it with a blood pressure cuff infl ated above systolic pressure, which rapidly normalised the left eye intraocular pressure (video). The fi stula was tied off in theatre. At 5 week follow-up acute ophthalmic signs had resolved. Some blot haemorrhages of the left fundus remained, but these did not aff ect the patient’s vision. On re-examination of his medical records, we saw that 1 year earlier he had undergone declotting of the left forearm fi stula and venography at the time had shown left brachiocephalic vein occlusion. He had previously had central lines inserted on both sides, which probably contributed to the occlusion. After 13 months of successful peritoneal dialysis the patient died from complications of sepsis. Arterialised blood fl ow within the cavernous sinus causes an ocular bruit, pulsating exophthalmos, diplopia, conjunctival chemosis, orbital pain, dilated and arterialised conjunctival vessels, raised intraocular pressure, and proptosis. This is most commonly due to carotid cavernous fi stulas, dural venous fi stulas, and arteriovenous malformations. Similar symptoms caused by haemodialysis shunts have been reported. Preexisting ipsilateral brachiocephalic vein occlusion, in which restriction of venous return via the brachiocephalic vein caused blood to be redirected into the jugular system, was present both in our case and a previous report of a patient with an upper limb fi stula. Central venous occlusion can be caused by malignancy or central venous catheterisation, although patients with peripheral haemodialysis arteriovenous shunts can have brachiocephalic vein occlusion without preceding central venous catheterisation. In our case, the central vein occlusion was probably caused by the combination of having had central lines inserted in the past and the presence of the arteriovenous fi stula itself. The anatomical location of the fi stula probably contributed to the aberrant venous fl ow because the pressure in the upper arm fi stula was higher than that in the forearm arteriovenous fi stula. Sight-threatening intraocular pressure due to an upper arm dialysis fi stula