Hum Chung

Risk factors associated with sclerotomy leakage and postoperative hypotony after 23-gauge transconjunctival sutureless vitrectomy.

Purpose: To investigate the incidence and risk factors of sclertomy leakage and postoperative hypotony after 23-gauge transconjunctival sutureless vitrectomy. Methods: This was a retrospective study including 322 eyes of 292 patients who underwent 23-gauge transconjunctival sutureless vitrectomy by a single surgeon with minimum follow-up period of 1 month. The incidence and risk factors of intraoperative suture placement for leaking sclerotomies and postoperative hypotony (≤5 mmHg) were analyzed in association with seven clinical factors. Results: Intraoperative suture placement was required for leaking sclerotomies in 36 cases (11.2%) and was related to prior vitrectomy (OR = 7.5), young age (<50 years) at operation (OR = 4.9), and vitreous base dissection (OR = 3.5). The incidences of postoperative hypotony were 11.3% at 2 hours, 6.5% at 5 hours, 3.8% at 1 day, and 0% at 1 week. Myopia and gas tamponade were associated with early postoperative hypotony. No complications developed related to sclerotomy leakage or postoperative hypotony. Conclusions: The risk factors of intraoperative sclerotomy leakage requiring suture placement after 23-gauge transconjunctival sutureless vitrectomy are prior vitrectomy, a young age at operation, and vitreous base dissection. Caution should be exercised to ensure the detection of sclerotomy leakage and hypotony in cases with these risk factors.

Combined surgery and sequential surgery comprising phacoemulsification, pars plana vitrectomy, and intraocular lens implantation: comparison of clinical outcomes.

Purpose: To evaluate the effectiveness and safety of combined phacoemulsification, pars plana vitrectomy (PPV), and intraocular lens (IOL) implantation in diabetic and nondiabetic patients and compare the clinical results with those of sequential surgery. Setting: Seoul National University College of Medicine, Seoul, South Korea. Methods: The results of combined phacoemulsification, PPV, and IOL implantation in 52 patients (52 eyes) were retrospectively analyzed. The main outcome measures were preoperative and postoperative best corrected visual acuity (BCVA), postoperative BCVA of 20/40 or better, and intraoperative and postoperative complications. Combined surgery and sequential surgery were also compared using the same outcome measures. Results: Postoperatively, the BCVA was better in 44 eyes (84.6%); 12 eyes (23.1%) achieved a BCVA of 20/40 or better. Postoperative complications consisted of a transient intraocular pressure increase in 29 eyes (55.8%), hyphema in 10 (19.2%), neovascular glaucoma in 8 (15.4%), anterior chamber fibrin exudation in 7 (13.5%), vitreous hemorrhage in 7 (13.5%), retinal detachment in 3 (5.8%), and posterior capsule opacification in 1 (1.9%). In the diabetic patients, postoperative visual outcomes between the combined‐surgery group and the sequential‐surgery group were not significantly different; however, neovascular glaucoma occurred only in the combined‐surgery group. Other complications were not different between the combined‐surgery group and the sequential‐surgery group. In the nondiabetic patients, the postoperative visual outcomes and complications between the 2 groups were not significantly different. Conclusion: Combined phacoemulsification, PPV, and IOL implantation was safe and effective in selected patients, with the clinical outcomes comparable to those of sequential surgery.

A suprachoroidal electrical retinal stimulator design for long-term animal experiments and in vivo assessment of its feasibility and biocompatibility in rabbits.

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes.

CD8brightCD56+ T Cells Are Cytotoxic Effectors in Patients with Active Behçet’s Uveitis

Behçet’s uveitis, characterized by chronic recurrent uveitis and obliterating retinal vasculitis, frequently causes bilateral blindness. Intraocular infiltration of TCRαβ+CD8brightCD56+ cells was a distinct feature in Behçet’s uveitis. However, phenotypic natures and effector functions of the cells have remained elusive. This study was conducted to determine phenotypic and functional characteristics and cytotoxic mechanisms of CD8brightCD56+ T cells in Behçet’s uveitis. CD11b+CD27−CD62L− phenotypes of CD8brightCD56+ T cells were increased in patients with active Behçet’s uveitis compared with inactive Behcet’s patients and normal controls. Interestingly, CD45RAdimCD45RO− phenotypes were expanded, and CD94 expression was markedly up-regulated in contrast to the down-regulation of NKG2D. Furthermore, these subsets were polarized to produce IFN-γ and contained high amounts of preformed intracellular perforin while exclusively expressing surface FasL upon PI stimulation. Moreover, the cytolytic functions of freshly isolated CD8brightCD56+ T cells were up-regulated against both K562 (NK-sensitive) and Raji (NK-resistant) cells, which were effectively inhibited by perforin inhibitor (concanamycin A). Their cytolytic activity against HUVECs was also increased and was effectively suppressed by Fas ligand inhibitor (brefeldin A) and partly by perforin inhibitor. Furthermore, cytolytic functions of PMA and ionomycin-stimulated CD8brightCD56+ T cells against HUVECs were greatly enhanced, by pretreatment of recombinant human IFN-γ on HUVECs. Therefore, CD8brightCD56+ T cells in Behçet’s uveitis are characterized by cytotoxic effector phenotypes with functional NK receptors and function as strong cytotoxic effectors through both Fas ligand-dependent and perforin-dependent pathways.

Radiosurgery of intracranial cavernous malformations.

Summary. Background: The efficacy of radiosurgery in cases of surgically high risk symptomatic cavernous malformations (CMs) for reducing haemorrhagic risk and for seizure control has not been clearly documented and the radiation-induced complications of radiosurgery remain problematic. The authors present a retrospective clinical analysis of 22 cases of CMs treated by radiosurgery. Methods: Twenty-two patients with symptomatic CMs were treated by linear accelerator (LINAC) radiosurgery or Gamma knife (GK) between 1995 and 1998. Medical records including radiological investigations were carefully reviewed to the last follow-up. The mean age of the patients was 34.1 years (12–56) and the male to female ratio was 12:10. Twenty patients reported at least one episode of bleeding and four had undergone microsurgery before radiosurgery. The remaining two patients presented with seizure without evidence of recent haemorrhage. In 16 cases, the CMs were deep-seated, and the others were located in the cerebral hemispheres; four were located at an eloquent area. LINAC radiosurgery using computed tomography scan was performed in 11 cases until May 1997, after which GK radiosurgery using magnetic resonance (MR) image was performed in 11 cases. The volume of the lesion ranged from 0.09 cc to 4.8 cc (mean 1.42 cc) and the mean marginal dose was 16.1 Gy (8–24). The median follow-up period after radiosurgery was 38.3 months (21–67). The rate of haemorrhage, seizure, and neurological deterioration following radiosurgery was analyzed, and the rate of haemorrhage was compared to that seen in natural course reports. Findings: There was one case of haemorrhage during the follow-up period and the seizure was well controlled with anticonvulsants. In the group with prior haemorrhage, the bleeding rate of cavernous malformation after radiosurgery (1.55%/year) was lower than that of pre-radiosurgical period (35.5%/year, t=1.296, P=0.04). Six patients showed neurological deterioration following radiosurgery, however, the neurological deficits persisted in only two of the patients with LINAC. The radiosurgical modality (LINAC vs. GK) showed a possible correlation to radiation induced neurological deficits (P=0.06). On the MR images at the last follow-up, the lesion was decreased in eleven patients, increased in one, and no change was found in 10 cases. The T2 weighted MR images revealed a perilesional high signal change in nine patients. This signal change was not statistically related to lesion size (P=0.236), location (P=0.658), nor radiation dose (P=0.363), but was dependent on the treatment modality (P=0.02). New-enhancing lesion and a new cyst were each found in one case, respectively, during the follow-up. Interpretation: Radiosurgery may be a good alternative option for treatment of surgically high risk CMs. However, the optimal radiosurgical technique, dose adjustment, and proper delineation of the mass are prerequisites. Radiosurgery induced complications are still problematic and post-radiosurgery MR image changes need to be further elucidated.

Long-term Temporal Changes of Macular Thickness and Visual Outcome after Vitrectomy for Idiopathic Epiretinal Membrane

PURPOSE To evaluate the long-term correlation of visual outcome and macular thickness after vitrectomy for idiopathic epiretinal membrane and to identify prognostic factors for good visual outcome. DESIGN Retrospective, observational case series. METHODS We reviewed the records of 52 patients with idiopathic epiretinal membrane who were treated with vitrectomy and could be followed up for more than 12 months. The main outcome measures were best-corrected visual acuity (BCVA) and central macular thickness at baseline; at 1, 3, 6, and 12 months after surgery; and at the final follow-up visit. The correlation between BCVA and central macular thickness was analyzed and the receiver operating characteristic curve analysis was performed to obtain cutoff values for visual prognosis. RESULTS Most of the changes in BCVA and central macular thickness took place during the first 3 months and reached a plateau at 12 months after surgery. Despite the lack of changes in BCVA after 12 months of follow-up, significant reduction in central macular thickness could still be observed over 12 months after surgery. The final BCVA was correlated significantly with preoperative BCVA and central macular thickness and early postoperative central macular thickness. Among them, the postoperative central macular thickness at 1 month showed the largest area under the receiver operating characteristic curve. CONCLUSIONS Given the removal of the confounding effect of cataract, postoperative follow-up of 12 months may be sufficient to reach the final BCVA after surgery. However, more time is needed to achieve final central macular thickness. Because of the significant correlation between final BCVA and early postoperative central macular thickness, serial optical coherence tomography images in the early postoperative period were needed to predict visual outcome after epiretinal membrane removal.

AKAP12 Regulates Human Blood–Retinal Barrier Formation by Downregulation of Hypoxia-Inducible Factor-1α

Many diseases of the eye such as retinoblastoma, diabetic retinopathy, and retinopathy of prematurity are associated with blood–retinal barrier (BRB) dysfunction. Identifying the factors that contribute to BRB formation during human eye development and maintenance could provide insights into such diseases. Here we show that A-kinase anchor protein 12 (AKAP12) induces BRB formation by increasing angiopoietin-1 and decreasing vascular endothelial growth factor (VEGF) levels in astrocytes. We reveal that AKAP12 downregulates the level of hypoxia-inducible factor-1α (HIF-1α) protein by enhancing the interaction of HIF-1α with pVHL (von Hippel-Lindau tumor suppressor protein) and PHD2 (prolyl hydroxylase 2). Conditioned media from AKAP12-overexpressing astrocytes induced barriergenesis by upregulating the expression of tight junction proteins in human retina microvascular endothelial cells (HRMECs). Compared with the retina during BRB maturation, AKAP12 expression in retinoblastoma patient tissue was markedly reduced whereas that of VEGF was increased. These findings suggest that AKAP12 may induce BRB formation through antiangiogenesis and barriergenesis in the developing human eye and that defects in this mechanism can lead to a loss of tight junction proteins and contribute to the development of retinal pathologies such as retinoblastoma.

The clinical and ocular manifestations of Takayasu arteritis.

Purpose To evaluate the clinical and ocular manifestations of Takayasu arteritis and the fundus fluorescein angiography (FFA) characteristics of Takayasu retinopathy (TR). Patients and Methods Medical records and fundus fluorescein angiograms of 156 eyes of 78 patients with Takayasu arteritis were reviewed. Fundus FA using a wide-field fundus camera (60°) was performed in 19 patients, and conventional angiography or spiral computed tomographic angiography was performed in all 78 patients. Results The series included 67 female and 11 male patients; mean age at time of diagnosis was 26.7 years (range, 4–61 years). Hypertension was found in 44 (56.4%) patients, ischemic cerebrovascular symptoms in 18 (23.1%) patients, and amaurosis fugax in 20 (25.6%) patients. On fundus examination, no retinopathy was found in 87 (55.8%) eyes; hypertensive retinopathy was found in 48 (30.8%) eyes; and TR was found in 21 (13.5%) eyes. Patients with TR had carotid artery or aortic arch involvement, and patients with hypertensive retinopathy had involvement of the descending aorta or renal artery and sparing of the carotids. Best-corrected visual acuity in TR Stage 1 to 3 ranged from 20/15 to 20/30, but in Stage 4, it ranged from 20/200 to hand motions because of secondary ocular complications. On FFA, the arm-to-retina circulation time was prolonged in all 21 eyes with TR (mean, 22.7 ± 8.9 seconds), but only 14 eyes showed delayed arteriovenous filling time, which was mainly found in chronic, moderate to severe TR, Stage 3 or 4. Arteriovenous anastomosis was found in all 12 eyes with Stage 3 and 4 TR. Conclusions Delayed arm-to-retina circulation time is shown in all cases of TR, but delayed arteriovenous filling time is mostly found in moderate and severe TR. During ophthalmic examination, the delay of arteriovenous filling time and formation of arteriovenous anastomosis must be examined carefully to prevent visual deterioration.

Morphologic photoreceptor abnormality in occult macular dystrophy on spectral-domain optical coherence tomography.

PURPOSE. To investigate morphologic photoreceptor layer abnormalities and their correlation with visual function in occult macular dystrophy (OMD), by using spectral-domain optical coherence tomography (SD-OCT). METHODS. This observational case series included 18 eyes of 9 patients with OMD. All patients underwent an ophthalmic evaluation, which included a fundus examination, fluorescein angiography, full-field electroretinography (ERG), multifocal ERG, time-domain optical coherence tomography (TD-OCT), and visual field testing. Morphologic photoreceptor layer abnormalities of the retinal layers were investigated with SD-OCT. The structure-function relationship was investigated regarding visual acuity, symptom duration, and multifocal ERG RESULTS: RESULTS. Best corrected visual acuity ranged from 20/200 to 20/20. Four patients had a symmetric decline of acuity in both eyes (20/200-20/100), and five had unilateral vision impairment (20/200-20/50). TD-OCT showed foveal thinning in all patients, but revealed no other retinal layer abnormality. In 15 eyes of 8 patients, SD-OCT demonstrated a well-defined disruption of the inner segment-outer segment (IS-OS) junction of the photoreceptors and of the Verhoeff membrane (cone outer segment tips). SD-OCT showed that three of five patients with presumed unilateral OMD had bilateral OMD after initial or follow-up examinations. Degrees of abnormality in the photoreceptor layer varied and correlated with visual acuity and symptom duration. CONCLUSIONS. SD-OCT can demonstrate the disruption of photoreceptors in most patients with OMD and the morphologic changes on SD-OCT correlate with visual function and disease progression. These morphologic abnormalities can be an important feature and cause of vision loss in patients with OMD.

Development of microelectrode arrays for artificial retinal implants using liquid crystal polymers.

PURPOSE To develop a liquid crystal polymer (LCP)-based, long-term implantable, retinal stimulation microelectrode array using a novel fabrication method. METHODS The fabrication process used laser micromachining and customized thermal-press bonding to produce LCP-based microelectrode arrays. To evaluate the fabrication process and the resultant electrode arrays, in vitro reliability tests and in vivo animal experiments were performed. The in vitro tests consisted of electrode site impedance recording and electrode interlayer adhesion monitoring during accelerated soak tests. For in vivo testing, the fabricated electrode arrays were implanted in the suprachoroidal space of rabbit eyes. Optical coherence tomography (OCT) and electrically evoked cortical potentials (EECPs) were used to determine long-term biocompatibility and functionality of the implant. RESULTS The fabricated structure had a smooth, rounded edge profile and exhibited moderate flexibility, which are advantageous features for safe implantation without guide tools. After accelerated soak tests at 75 degrees C in phosphate-buffered saline, the electrode sites showed no degradation, and the interlayer adhesion of the structure showed acceptable stability for more than 2 months. The electrode arrays were safely implanted in the suprachoroidal space of rabbit eyes, and EECP waveforms were recorded. Over a 3-month postoperative period, no chorioretinal inflammation or structural deformities were observed by OCT and histologic examination. CONCLUSIONS LCP-based flexible microelectrode arrays can be successfully applied as retinal prostheses. The results demonstrate that such electrode arrays are safe, biocompatible, and mechanically stable and that they can be effective as part of a chronic retinal implant system.