Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations.

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03-0.15Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade. In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0°C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF-CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p<0.05). Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA. Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation.

Autonomic blockade during sinusoidal baroreflex activation proves sympathetic modulation of cerebral blood flow velocity.

BACKGROUND AND PURPOSE: Pharmacological blockade showed sympathetic origin of 0.03 to 0.15 Hz blood pressure (BP) oscillations and parasympathetic origin of 0.15 to 0.5 Hz RR-interval (RRI) oscillations, but has not been used to determine origin of cerebral blood flow velocity (CBFV) oscillations at these frequencies. This study evaluated by pharmacological blockade whether 0.1 Hz CBFV oscillations are related to sympathetic and 0.2 Hz CBFV oscillations to parasympathetic modulation. METHODS: In 11 volunteers (24.6 ± 2.3 years), we monitored RRIs, BP, and proximal middle cerebral artery CBFV, at rest, during 180 s sympathetic BP activation by 0.1 Hz sinusoidal neck suction (NS), and during 180 s parasympathetic RRI activation by 0.2 Hz NS. We repeated recordings after 25 mg carvedilol, and after 0.04 mg/kg atropine. Autoregressive analysis quantified RRI-, BP-, and CBFV-spectral powers at 0.1 Hz and 0.2 Hz. We compared parameters at rest, during 0.1 Hz, or 0.2 Hz NS, with and without carvedilol or atropine (analysis of variance, post hoc testing; significance, P<0.05). RESULTS: Carvedilol significantly increased RRIs and lowered BP, CBFV, and 0.1 Hz RRI-, BP-, and CBFV-powers at baseline (P=0.041 for CBFV-powers), and during 0.1 Hz NS-induced sympathetic activation (P<0.05). At baseline and during 0.2 Hz NS-induced parasympathetic activation, atropine lowered RRIs and 0.2 Hz RRI-powers, but did not change BP, CBFV, and 0.2 Hz BP- and CBFV-powers. CONCLUSIONS: Attenuation of both 0.1 Hz CBFV and BP oscillations after carvedilol indicates a direct relation between 0.1 Hz CBFV oscillations and sympathetic modulation. Absent effects of atropine on BP, CBFV, and 0.2 Hz BP and CBFV oscillations suggest that there is no direct parasympathetic influence on 0.2 Hz BP and CBFV modulation.

Split cornea transplantation: relationship between storage time of split donor tissue and outcome.

PURPOSE: To analyze the relationship between storage time of split donor tissue and outcomes after deep anterior lamellar keratoplasty (DALK) and Descemet's membrane endothelial keratoplasty (DMEK). DESIGN: Retrospective analysis of a nonrandomized, consecutive, interventional case series. PARTICIPANTS: One hundred ten eyes with anterior stromal disease suitable for DALK and 110 eyes with endothelial disease suitable for DMEK underwent surgically successful split cornea transplantation combining both procedures within 7 days after splitting. METHODS: Split donor storage times (splitting to grafting) and total storage times (death to grafting) were correlated with the 1-year functional and morphologic outcomes after DALK and DMEK surgery using a Spearman correlation coefficient and a Mann-Whitney U test. MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity (BSCVA), endothelial cell density, and complication rates within 12 months of follow-up. RESULTS: The mean split donor storage time was 35 ± 47 hours (range, 0-162 hours) after splitting for anterior donor grafts and 21 ± 40 hours (range, 0-158 hours) for posterior grafts. The mean total storage time was 352 ± 108 hours (range, 108-678 hours) for anterior lamellas and 339 ± 109 hours (range, 96-630 hours) for posterior lamellas. One year after DALK, the mean BSCVA was 20/30 (range, 20/50-20/20), endothelial cell loss was 8% (range, 2%-16%), and the complication rate (Descemet's folds, epitheliopathy, loose sutures) was 18%. One year after DMEK, the mean BSCVA was 20/25 (range, 20/40-20/16), endothelial cell loss was 41% (range, 17%-63%), and the complication rate (partial graft detachment) was 62%. For DALK and DMEK, no significant association was observed between split donor storage time as well as total storage time and BSCVA (P ≥ 0.409), endothelial cell loss (P≥0.236), or complication rate (P ≥ 0.647) within 1 year of follow-up. CONCLUSIONS: Anterior and posterior donor tissue may be stored safely for up to 1 week in organ culture before use in DALK and DMEK surgery. This simplifies the clinical feasibility of split cornea transplantation to reduce donor shortage and cost in corneal transplantation in the future. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Microbubble incision as a new rescue technique for big-bubble deep anterior lamellar keratoplasty with failed bubble formation.

PURPOSE: To describe a new surgical technique allowing dissection down to Descemet membrane in big-bubble deep anterior lamellar keratoplasty (DALK) with failed big-bubble formation (the "microbubble incision technique"). METHODS: This is an interventional case series of 10 consecutive patients with keratoconus undergoing intended big-bubble DALK with failure to establish a normal big bubble. In all patients, repeated air injections into the stroma were performed, leaving a whitish colored stroma. Lamellar dissection as far down as possible was then performed within this white tissue. As soon as the anterior chamber was visible, a large remaining intrastromal air bubble was incised with a sharp 15-degree knife introduced perpendicular to the tissue to open up this predescemetic bubble. If deeper air bubbles were still visible, this approach was repeated. Using a blunt spatula, this new layer was then prepared and viscodissection performed. RESULTS: Using this novel approach, in 9 of the 10 patients, it was possible to dissect down to Descemet membrane. Macroperforation made conversion to penetrating keratoplasty necessary in 1 patient. Microperforations not necessitating conversion occurred in 2 patients. All 9 patients with "rescued" DALK had an uneventful postoperative course and had a mean visual acuity of 20/63 ± 20/125 (range, 20/500-20/50) and a mean endothelial cell count of 1672 ± 163 cells per square millimeter (range, 1493-1867 cells/mm) at 3 months. CONCLUSIONS: Microbubble incision is a new rescue technique for big-bubble DALK patients without bubble formation allowing for a safer dissection down to Descemet membrane.

Pentacam-based big bubble deep anterior lamellar keratoplasty in patients with keratoconus.

PURPOSE: To describe the clinical results of Pentacam-based big bubble deep anterior lamellar keratoplasty (DALK) to achieve an intended 90% depth of initial lamellar trephination. METHODS: Fifty consecutive eyes of 50 patients with keratoconus, keratoglobus, and anterior stromal scars were included. DALK was performed with the big bubble technique using a 90% intended depth for initial lamellar trephination based on preoperative pachymetry by Pentacam. Main outcome measures were success of surgery, best spectacle-corrected visual acuity, endothelial cell count, refractive astigmatism at 12-month follow-up, and rate of intra- and postoperative complications. RESULTS: In 84% of the patients (n = 42), Pentacam-based big bubble DALK could be performed successfully. Successful big bubble formation could be achieved in 80% of the patients (n = 34). In case of macroperforation (n = 8), surgery was converted to standard penetrating keratoplasty representing a conversion rate of 16%. Intraoperative microperforation (n = 5) could be handled by an intracameral air injection at the end of operation with successful completion of the lamellar procedure. No allograft rejection was observed. Best spectacle-corrected visual acuity improved from 20/125 ± 20/160 preoperatively to 20/40 ± 20/80 at 12-month follow-up. Endothelial cell count was 2102 ± 318 cells per square millimeter preoperatively and 1735 ± 420 cells per square millimeter at 12-month follow-up. Refractive astigmatism was 7.09 ± 3.13 diopters preoperatively and decreased to 4.13 ± 2.41 diopters. CONCLUSION: Pentacam-based big bubble DALK using a 90% intended depth of initial lamellar trephination seems to be a safe and effective procedure for anterior corneal stromal disorders such as keratoconus. We suggest that Pentacam-based depth assessment allows for reliably deep initial preparation and may allow more successful bubble formation in DALK surgery.

Split cornea transplantation for 2 recipients - review of the first 100 consecutive patients.

PURPOSE: To evaluate the feasibility of split cornea transplantation for 2 recipients by combining deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK). DESIGN: Interventional case series. METHODS: Fifty consecutive eyes with anterior stromal disease suitable for DALK and 50 eyes with endothelial disease suitable for DMEK were scheduled for split cornea transplantation combining both procedures within 72 hours. Main outcome measures included success of using a single donor cornea for 2 recipients, best spectacle-corrected visual acuity (BSCVA), and complication rates within 6 months' follow-up. RESULTS: A single donor cornea could be used for 2 recipients in 47 cases (94%). In 3 eyes (6%), the DALK procedure had to be converted to penetrating keratoplasty (PK) requiring a full-thickness corneal graft. Thereby, 47 donor corneas (47%) could be saved. Six months after surgery, mean BSCVA was 20/36 in the 47 eyes that underwent successful DALK, 20/50 in the 3 eyes that underwent conversion from DALK to PK, and 20/29 in the 50 eyes that underwent DMEK. Postoperative complications after DALK included Descemet folds in 5 eyes (11%) and epitheliopathy in 3 eyes (6%). After DMEK, partial graft detachment occurred in 26 eyes (52%) and was managed successfully with intracameral air reinjection. All corneas remained clear up to 6 months after surgery. No intraocular infections occurred. CONCLUSION: Split use of donor corneal tissue for combined DALK and DMEK procedures in 2 recipients within 3 subsequent days is a feasible approach to reduce donor shortage in corneal transplantation in the future.

A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty.

PURPOSE: Lamellar techniques for selective replacement of diseased corneal structures have recently been improved. Descemet membrane endothelial keratoplasty (DMEK) allows the sole replacement of the endothelium--Descemet membrane layer (EDM). However, wide-spread use of DMEK is currently limited because of problems with donor preparation namely the tearing of the Descemet membrane and the difficulty to unfold the EDM graft in the anterior chamber (AC). METHODS: A standardized DMEK procedure that allows safe preparation of EDM, atraumatic introduction of EDM into the AC, reliable orientation of EDM during surgery, and stepwise unfolding within the AC is described in 80 patients. Visual acuity and corneal endothelial cell density were assessed. RESULTS: A stepwise approach using a novel bimanual underwater technique to harvest EDM from donor corneal buttons allows reproducible generation of grafts without tearing the Descemet membrane. Injection of the EDM roll into the AC is achieved by use of a standard injector cartridge, whereas the depth of AC is maintained by an irrigation handpiece. Marks at the margin of EDM allow orientation. Finally, unfolding EDM in the AC is achieved by sequential use of water jets and air bubbles. In the early phase of the learning curve, 4 patients were regrafted because of graft failure. Endothelial cell density decreased from 2600 6 252 to 1526 6 341 cells per square millimeter 1 month after DMEK. CONCLUSIONS: A novel technique for graft preparation and EDM injection results in improved safety with a high rate of successful DMEKs.

Split cornea transplantation for 2 recipients: a new strategy to reduce corneal tissue cost and shortage.

PURPOSE: To evaluate the feasibility of using a single donor cornea for 2 recipients by combining deep anterior lamellar keratoplasty (DALK) and Descemet's membrane endothelial keratoplasty (DMEK) surgeries on the same day. DESIGN: Single-center, nonrandomized, prospective, interventional case series. PARTICIPANTS: Twelve consecutive donor corneas were scheduled for split cornea transplantation combining DALK for a keratoconus patient and DMEK for a Fuchs' endothelial dystrophy patient on the same surgery day. METHODS: First, a big-bubble DALK procedure was performed for the keratoconus eye. When bare Descemet's membrane was prepared successfully requiring no conversion to penetrating keratoplasty (PK), then during surgery the donor, endothelium-Descemet's membrane layer was removed and stored for subsequent DMEK in a second patient, and the remaining anterior lamella of the donor cornea was used to complete the DALK surgery. Afterward, a DMEK procedure was performed on the second patient with Fuchs' endothelial dystrophy, grafting the stored endothelium-Descemet's membrane layer of the original donor button. MAIN OUTCOME MEASURES: Success of using a single donor cornea for 2 recipient eyes, best spectacle-corrected visual acuity (BSCVA), and complication rates within 6 months follow-up. RESULTS: A single donor cornea could be used for 2 recipients in 10 of 12 donor buttons (83%). In 2 cases (17%), the DALK procedure had to be converted to PK requiring a full-thickness corneal graft. Therefore, 10 donor corneas (45%) could be saved. Six months after surgery, mean BSCVA was 20/35 (range, 20/50-20/25) in 10 eyes that underwent successful DALK, 20/50 (range, 20/63-20/40) in 2 eyes that underwent conversion from DALK to PK, and 20/31 (range, 20/50-20/16) in 10 eyes that underwent DMEK. Postoperative complications after DALK included Descemet's folds in 3 eyes (30%) and epitheliopathy in 2 eyes (20%). After DMEK, partial graft detachment occurred in 5 eyes (50%) and was managed successfully with intracameral air reinjection. All corneas remained clear up to 6 months after surgery. CONCLUSIONS: Split use of donor corneal tissue for combined DALK and DMEK procedures in 2 recipients on the same surgery day is a promising strategy to reduce donor shortage and cost in corneal transplantation surgery in the future.