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Purpose: To compare refractive outcomes of the foldable intraocular lens sutureless scleral fixated sutureless (Carlevale® FIL-SSF) with the iris-claw lens (Artisan®)., Methods: This retrospective study included consecutive patients who underwent a FIL-SSF implantation or an iris-claw implantation between January 2020 and November 2022 in the ophthalmology departments of Hospices Civils de Lyon (France)., Results: A total of 271 eyes from 265 patients were included: 96 eyes in the FIL-SSF group and 175 eyes in the iris-claw group. At 6 months, the mean (SD) surgically induced astigmatism (SIA) was significantly lower in the FIL-SSF group with 0.3 (1.8) diopters against 0.8 (2.1) diopters in the iris-claw group (p = 0.01). The mean (SD) refractive error was also lower for the FIL-SSF group with 0.1 (1.2) diopters versus 0.5 (1.6) diopters in the iris-claw group (p < 0.001). The mean best corrected visual acuity at 6 months was not significantly different between FIL-SSF and iris-claw lens with 0.47 (0.58) logMAR and 0.39 (0.55) logMAR, respectively (p = 0.12). However, the mean (SD) operative time was longer for FIL-SSF implantation in comparison to iris-claw implantation (59.8 (21.1) minutes versus 41.9 (24.4) minutes, respectively (p < 0.001)). The rate of postoperative complications was similar between the two techniques., Conclusion: This study shows that FIL-SSF achieves better refractive results than iris-claw lens, with a similar rate of postoperative complications. As a relatively new implantation technique, there is a learning curve required to reduce operating time., Key Messages: What is known? Multiple surgical options for correcting aphakia in the absence of capsular support can be used. Currently, foldable intraocular lens sutureless scleral fixated sutureless (FIL-SSF, Carlevale®) and iris-claw (Artisan®) implants are the two preferred options, but there is no consensus on the best technique to adopt. What is new? We showed that FIL-SSF has a significantly lower surgically induced astigmatism compared to the iris-claw implant. Similar rate of postoperative complications was found between these two techniques. Future studies with a longer follow-up period are needed to ascertain its tolerance., Competing Interests: Declarations Ethical approval An international review board approved the study (Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Société Française d’Ophtalmologie IRB#1). Informed consent Informed consent was obtained from all individual participants included in the study. Disclosure of potential conflicts of interest No Conflicts of Interest.All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Research involving human participants All procedures performed in studies involving human participants were in accordance with the ethical standards of the French Society of Ophthalmology, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Competing interests The authors declared no potential conflicts of interest., (© 2024. The Author(s).)

Purpose: To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse., Methods: This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group., Results: A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months., Conclusion: The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

Purpose: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids., Methods: We included 39 BSCR patients that were followed for ≥1 year. We analyzed their progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. In order to determine the efficiency of initial loading doses, patients were classified into two groups according to their initial treatment: methylprednisolone followed by prednisone (n = 28) and prednisone alone (n = 11)., Results: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day., Conclusions: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

Purpose: To evaluate mean change in best-corrected visual acuity (BCVA) at 52 weeks in patients with inflammatory choroidal neovascularization (CNV) treated with aflibercept., Methods: We conducted a prospective non-comparative open-label trial. Following one mandatory intravitreal injection of aflibercept, patients were treated under a pro re nata (PRN) dosing regimen with monthly visits., Results: A total of 19 patients were included, but one presented exclusion criteria; 16 patients were followed for the whole 52-week study, and data for the primary endpoint analysis were available for 14. At baseline, mean BCVA and mean central retinal thickness (CRT) were 64.53 (±19.64) letters and 351.79 (±97.77) μm, respectively. At 52 weeks, the mean change in BCVA was +9.50 (±12.90) letters [95%CI = +2.05-+16.95]. One patient had lost more than 15-letters at 24 weeks, and another one at 52 weeks. CRT change was -62.77 (±100.73) μm at 24 weeks and -66.53 (±97.47) μm at 52 weeks. There was a mean number of 3.56 (±3.29) intravitreal injections at 52 weeks (min = 1; max = 12). No serious ocular adverse events related to the treatment were reported., Conclusions: Our study shows that aflibercept is clinically effective, both anatomically and functionally in the treatment of inflammatory CNV. Following the first injection, the PRN strategy appears sufficient for treating most choroidal neovessels., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Introduction: The aim of this study was to evaluate the effect of initial treatment regimen individualization (pro re nata or treat-and-extend [TAE]), according to macular neovascularization (MNV) subtype, on the functional and anatomical response in neovascular age-related macular degeneration (nAMD). The secondary objective was to compare the treatment burden between each MNV subtype., Methods: Consecutive treatment-naïve nAMD patients were retrospectively included. MNV subtype was graded by 2 independent blinded investigators on multimodal imaging. Functional and anatomical outcomes were analysed according to treatment regimen and MNV subtypes., Results: A total of 281 eyes from 243 patients were included in the study. According to the treatment regimen, there was no significant difference in best-corrected visual acuity gain within the first 2 years of treatment for type 1 (p = 0.106) and type 3 MNV (p = 0.704). Conversely, there was a significant difference in favour of TAE regimen for type 2 (p = 0.017) and type 4 MNV (p = 0.047). Type 1 MNV had a higher proportion of visits with subretinal fluid (p = 0.0007) but not with intraretinal fluid (p = 0.22). The mean interval between the last 2 injections was significantly shorter for type 1 MNV (p = 0.0045)., Conclusion: The individualization of the initial treatment protocol according to MNV subtype can improve the functional outcome and may decrease the treatment burden., (© 2023 S. Karger AG, Basel.)

Diabetic macular edema (DME) is now a well-known condition for which a number of treatments have been shown to be effective. Intraocular corticosteroids are part of this therapeutic arsenal but are sometimes responsible for ocular hypertension. We describe here the case of a 60-year-old man with a history of bilateral DME who received an intravitreal injection of 190 µg fluocinolone acetonide (FAc) (ILUVIEN ® , Alimera Sciences, Alpharetta, GA, USA) who presented a persistent ocular hypertension in one eye despite FAc removal by pars plana vitrectomy and was successfully managed by Preserflo ® microshunt surgery., Competing Interests: Olivier Loria, Amina Rezkallah, and Samuel Chacun have no conflict of interest. Thibaud Mathis is a consultant for Abbvie, Bayer, GSK, Horus, and Novartis. Laurent Kodkijian is a consultant for Abbvie, Bayer, Horus, Novartis, Roche, and Thea. Philippe Denis is a consultant for Abbvie, Thea, Horus, and Santen., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Ocular metastases are the most frequent ocular malignant tumors; their prevalence is estimated around 5-10% and is even higher in patients with breast or lung cancer. They represent various clinical situations, but they share the same hierarchical multidisciplinary therapeutic challenge with respect to the way systemic and local therapies should be selected in combination or sequentially in the personalized medical history of a patient. The challenges include tumor control, eye preservation, and the minimization of iatrogenic damage to sensitive tissues surrounding the tumor in order to preserve vision. These aims should further contribute to maintaining quality of life in patients with metastases. Many patients with choroidal metastases have systemic molecular treatment for their primary tumor. However, secondary resistance to systemic treatment is common and may ultimately be associated with cancer relapse, even after an initial response. Therefore, it makes sense to propose local treatment concomitantly or after systemic therapy to provide a more sustainable response. The aim of this review is to present current therapeutic strategies in ocular metastases and discuss how to tailor the treatment to a specific patient.

Purpose: To evaluate choriocapillaris alterations following proton beam therapy irradiation using swept-source optical coherence tomography-angiography, and to assess their correlation with the grade of radiation retinopathy (RR)., Methods: Eyes with uveal melanoma evaluated before and after irradiation with proton beam therapy were included, as well as the healthy fellow eye. The gradation of RR was based on a previously published classification. Choriocapillaris flow voids area was analyzed using Phansalkar thresholding. Retinal vascularization was described by foveal avascular zone (FAZ) perimeter, FAZ area, FAZ circularity index, and percentage of nonperfusion area (PAN) in the superficial capillary plexus (SCP) or deep capillary plexus., Results: A total of 157 eyes of 83 patients were analyzed. Overall, there was a significant difference between the control group, the uveal melanoma before proton beam therapy group, and the grades of RR in the uveal melanoma after proton beam therapy group for FAZ perimeter ( P < 0.001), FAZ area ( P < 0.001), FAZ-circularity index ( P < 0.001), PAN-SCP ( P < 0.001), PAN-deep capillary plexus ( P < 0.001), and choriocapillaris flow voids area ( P < 0.001). Moreover, choriocapillaris flow voids area was significantly increased in the early stages of RR ( P = 0.003) and was further significantly correlated with FAZ perimeter ( P < 0.001), FAZ area ( P < 0.001), FAZ-circularity index ( P = 0.010), PAN-SCP ( P < 0.001), and PAN-deep capillary plexus ( P < 0.001)., Conclusion: Quantitative optical coherence tomography-angiography alterations in the choriocapillaris microvascularization are an early biomarker of RR and are correlated to the severity of the disease.

The eye is an exemplarily challenging organ to treat when considering ocular tumors. It is at the crossroads of several major aims in oncology: tumor control, organ preservation, and functional outcomes including vision and quality of life. The proximity between the tumor and organs that are susceptible to radiation damage explain these challenges. Given a high enough dose of radiation, virtually any cancer will be destroyed with radiotherapy. Yet, the doses inevitably absorbed by normal tissues may lead to complications, the likelihood of which increases with the radiation dose and volume of normal tissues irradiated. Precision radiotherapy allows personalized decision-making algorithms based on patient and tumor characteristics by exploiting the full knowledge of the physics, radiobiology, and the modifications made to the radiotherapy equipment to adapt to the various ocular tumors. Anticipation of the spectrum and severity of radiation-induced complications is crucial to the decision of which technique to use for a given tumor. Radiation can damage the lacrimal gland, eyelashes/eyelids, cornea, lens, macula/retina, optic nerves and chiasma, each having specific dose-response characteristics. The present review is a report of non-cancer effects that may occur following ionizing irradiation involving the eye and orbit and their specific patterns of toxicity for a given radiotherapy modality.

Purpose: Numerous small hyperreflective dots (HRDs) can be seen within the hyporeflective layer between the ellipsoid zone (EZ) and the interdigitation zone (IZ) on C-scan spectral-domain optical coherence tomography (SD-OCT) with a yet unknown variation under light conditions. The aim of this study was to explore light-induced SD-OCT changes in these HRDs., Methods: The study subjects were randomly assigned to two groups: Group 1 experienced a dark adaptation protocol followed by intense retinal photobleaching, while Group 2, serving as the control group, was exposed to constant ambient light without any variation. The number of HRDs was automatically counted., Results: Twenty healthy volunteers were prospectively included. The number of HRDs differed significantly over time (p = 0.0013). They decreased in Group 1 after dark adaptation and retinal photobleaching before returning to baseline levels 30 min later; conversely, they remained relatively constant in Group 2 throughout the study (p < 0.001). Light-skinned subjects had less HRD than dark-skinned subjects., Conclusion: We observed light-induced modifications in the space between the EZ and the IZ. We hypothesize that the HRDs visible in this zone correspond to melanosomes that are mobilized during the light stimulation protocol. Larger studies are recommended to further evaluate and confirm light-induced SD-OCT changes under physiological and pathological conditions., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Vitellogenesis in oviparous vertebrates is a critical marker of the restart of seasonal reproductive activity. During this process of multihormonal regulation, females allocate a considerable amount of organic and mineral reserves to the synthesis of yolk, with changes in their plasma values. In this work, we determined plasma levels of various metabolites and steroid hormones throughout the reproductive cycle in females of Salvator merianae who developed vitellogenic and non-vitellogenic follicular cycles. We worked for two consecutive years with 20 adult females from the Experimental Hatchery of the Facultad de Agronomía y Zootecnia of the Universidad Nacional de Tucumán. Values of metabolites: glucose, triglycerides, cholesterol, calcium, phosphorus, albumin, total proteins, and hormones: estradiol, progesterone, and testosterone, were determined during the following stages of the annual cycle: hibernation, hibernation emergence, courtship-mating, oviposition, and incubation. Vitellogenic females showed significantly higher plasma levels of triglycerides, calcium, phosphorus, and albumin than non-vitellogenic females, mainly in the courtship-mating stage (advanced vitellogenesis). In contrast, annual cholesterol averages were lower in vitellogenic females. Glucose showed changes throughout the annual cycle regardless of the vitellogenic condition. Total proteins plasma levels had very few fluctuations during the cycle. Among the hormones studied, only testosterone showed differences related to vitellogenic condition, with higher levels in non-vitellogenic females during the entire reproductive cycle. The knowledge of these changes associated with vitellogenesis will improve zootechnical management and will allow optimizing the reproductive efficiency of Salvator lizards in captivity.

Purpose: To evaluate quantitative alterations of the choriocapillaris in swept-source optical coherence tomography angiography in diabetic patients., Methods: We included normal patients and diabetic patients with and without diabetic retinopathy (DR), excluding patients with macular edema. Angiograms in 3 × 3 mm were acquired with Plexelite 9000 swept-source optical coherence tomography angiography. Choroidal flow voids were analyzed after removal of projection artifacts. The main evaluation was the correlation between choroidal flow voids area (FVA-CC) and DR stage., Results: A total of 120 eyes of 72 patients were analyzed. There were 17 eyes from healthy subjects, 30 eyes without DR, 22 eyes with minimal nonproliferative DR, 30 eyes with moderate nonproliferative DR, 16 eyes with severe nonproliferative DR, and 5 eyes with proliferative DR (PDR). The percentage of FVA-CC for each group was, respectively, 10.9 ± 3.4%, 14.6 ± 4.8%, 17.6 ± 3.5%, 20.7 ± 5.9%, 19.9 ± 2.9%, and 26.6 ± 4.4%. FVA-CC and DR stage significantly correlated (P < 0.0001). FVA-CC was significantly increased in diabetic patients without DR compared with healthy subjects (P = 0.008)., Conclusion: Diabetes is associated with quantifiable choriocapillaris alterations in swept-source optical coherence tomography angiography. These alterations precede clinical signs of DR and are correlated with DR stage.

The aim was to analyze the variations in macular vascularization on optical coherence tomography angiography (OCTA) according to the presence of intraretinal fluid (IRF) induced by exudative age-related macular degeneration (AMD). We included exudative AMD patients with IRF and/or subretinal fluid (SRF) and age-matched control eyes. All patients underwent a macular 6 × 6 mm swept-source OCTA. The mean perfusion density (MPD) and mean vascular density (MVD) were calculated in the superficial (SCP) and the deep (DCP) capillary plexus at two timepoints: during an episode of exudation (T0) and after its total resorption (T1). A total of 22 eyes in the IRF ± SRF group, 11 eyes in the SRF group and 11 eyes in the healthy group were analyzed. At T0, the IRF ± SRF group showed significantly lower MPD and MVD than healthy eyes in the SCP ( p < 0.001) and DCP ( p < 0.001). At T1, MPD and MVD significantly increased from T0 in the SCP ( p = 0.027 and p = 0.0093) and DCP ( p = 0.013 and p = 0.046) but remained statistically lower than in the healthy eyes. For the SRF group, only the DCP showed significantly lower MPD ( p = 0.012) and MVD ( p = 0.046) in comparison to the healthy eyes at T0. The present study shows that retinal vascular changes do occur in the case of exudative AMD.

Spondyloarthritis (Spa), Behçet's disease (BD) and sarcoidosis are major systemic inflammatory diseases worldwide. They are all multisystem pathologies and share a possible ocular involvement, especially uveitis. We hereby describe selected cases who were referred by ophthalmologists to our internal medicine department for unexplained uveitis. Physical examination and/or the use of laboratory and imaging investigations allowed to make a diagnosis of a systemic inflammatory disease in a large proportion of patients. In our tertiary referral center, 75 patients have been diagnosed with Spa ( n = 20), BD ( n = 9), or sarcoidosis ( n = 46) in the last two years. There was a significant delay in the diagnosis of Spa-associated uveitis. Screening strategies using Human Leukocyte Antigen (HLA)-B27 determination and sacroiliac magnetic resonance imaging in patients suffering from chronic low back pain and/or psoriasis helped in the diagnosis. BD's uveitis affects young people from both sexes and all origins and usually presents with panuveitis and retinal vasculitis. The high proportion of sarcoidosis in our population is explained by the use of chest computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography CT that helped to identify smaller hilar or mediastinal involvement and allowed to further investigate those patients, especially in the elderly. Our results confirm how in these sight- and potentially life-threatening diseases a prompt diagnosis is mandatory and benefits from a multidisciplinary approach.

Purpose : To identify prognosis factors and functional outcomes of persistent placoid maculopathy (PPM). Methods : We collected personal PPM cases and combined them with the data from the literature. Results : 68 eyes of 37 patients with PPM were analyzed, including six new cases. Twenty-six patients were men (70%) with a mean age of 51.8 years old. The mean initial visual acuity (VA) was 0.52 LogMar ± 0.55 for a mean final VA of 0.49 LogMar ± 0.51. Risk factors for poor VA included: initial VA less than 0.2 LogMar ( p < .0001), cardiovascular risk factor ( p = .008), autoimmune-related and/or systemic pro-inflammatory conditions ( p = .003), choroidal neovascularization ( p = .001), macular atrophy ( p = .03) and absence of systemic corticosteroid treatment ( p = .03). Conclusion : PPM is a choroidal inflammation. Identifying prognosis factors may help to guide treatment and follow-up. We showed that anti-inflammatory drugs, and anti-VEGF injections in cases of choroidal neovascularization, may lead to better outcomes.

Choroidal neovascularization (CNV) is a rare but severe complication in Best disease and autosomal recessive bestrophinopathy. However, the visualization of the neovascular membrane is difficult on fluorescein angiography (FA) and indocyanine green angiography (ICGA) because of dye leakage due to the accumulation of material. The authors' study reports a case series of pediatric Best disease where optical coherence tomography angiography (OCTA) contributed to the diagnosis of CNV and prompt treatment. Five eyes of three patients were included (two Best disease and one autosomal recessive bestrophinopathy). The mean age at diagnosis was 6.8 years ± 1.8 years (range: 5 years to 10 years). OCTA showed the typical "sea fan-shaped" neovascular membrane in all five eyes, whereas, in most cases, conventional imaging by FA and ICGA did not show clearly the neovascularization due to masking effect of the vitelliform material. OCTA seems to be a good alternative to diagnosing CNV in Best disease, especially in children, as it is a noninvasive, rapid technique for imaging, and does not require the administration of dyes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:597-601.]., (Copyright 2019, SLACK Incorporated.)

The most frequent site of ocular metastasis is the choroid. The occurrence of choroidal metastases has increased steadily due to the longer survival of metastatic patients and the improvement of diagnostic tools. Fundoscopy, ultrasonography, and fluorescein angiography are now complemented by indocyanine green angiography and optical coherence tomography. Choroidal tumor biopsy may also confirm the metastatic nature of the tumor and help to determine the site of the primary malignancy. There is currently no consensus on the treatment strategy. Most patients have a limited life expectancy and for these complex treatments are generally not recommended. However, recent advances in systemic therapy have significantly improved survival of certain patients who may benefit from an aggressive ocular approach that could preserve vision. Although external beam radiation therapy is the most widely used treatment, more advanced forms of radiotherapy that are associated with fewer side effects can be proposed in select cases. In patients with a shorter life expectancy, systemic therapies such as those targeting oncogenic drivers, or immunotherapy can induce a regression of the choroidal metastases, and may be sufficient to temporarily decrease visual symptoms. However, they often acquire resistance to systemic treatment and ocular relapse usually requires radiotherapy for durable control. Less invasive office-based treatments, such as photodynamic therapy and intravitreal injection of anti-VEGF, may also help to preserve vision while reducing time spent in medical settings for patients in palliative care. The aim of this review is to summarize the current knowledge on choroidal metastases, with emphasis on the most recent findings in epidemiology, pathogenesis, diagnosis and treatment., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To report the outcomes of initial methylprednisolone pulse then oral prednisone in the treatment of birdshot chorioretinopathy (BSCR)., Methods: We retrospectively reviewed medical records of 21 BSCR patients, treated with initial methylprednisolone, prednisone, or immunosuppressive therapy. Main outcome measures were changes in visual acuity, intraocular inflammation, concomitant immunosuppressive drug or intravitreal steroid, and adverse events., Results: In total, 14 patients were initially treated with methylprednisolone; four patients with prednisone; and three with immunosuppressive drug. Intraocular inflammation was controlled in 10 of 14 patients (71%) at 1 year, with a mean dose of 6.2 mg/day prednisone. Patients treated initially by methylprednisolone had improved visual acuity at 1 year, but it was not significantly different from patients treated initially by prednisone., Conclusions: Corticosteroid therapy, including initial methylprednisolone pulse then prednisone, was effective in stabilizing vision and decreasing inflammation in most patients with BSCR.

The zeta-associated protein of 70 kDa (ZAP-70) is expressed in patients with aggressive chronic lymphocytic leukemia (CLL). We found that ZAP-70+ CLL cells expressed activated heat-shock protein 90 (Hsp90) with high binding affinity for Hsp90 inhibitors, such as 17-allyl-amino-demethoxy-geldanamycin (17-AAG), whereas normal lymphocytes or ZAP-70- CLL cells expressed nonactivated Hsp90. Activated Hsp90 bound and stabilized ZAP-70, which behaved like an Hsp90 client protein only in CLL cells. Treatment with Hsp90 inhibitors such as 17-AAG and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) induced ZAP-70 degradation and apoptosis in CLL cells but not in T cells, and also impaired B-cell receptor signaling in leukemia cells. Transduction of ZAP-70- CLL cells with an adenovirus encoding ZAP-70 activated Hsp90 and specifically rendered the leukemia cells sensitive to 17-AAG. These data indicate that Hsp90 is necessary for ZAP-70 expression and activity; that ZAP-70 is unique among Hsp90 clients, in that its chaperone-dependency is conditional on the cell type in which it is expressed; and also that ZAP-70 is required for cell survival and signaling in CLL. Additionally, ZAP-70 expression in CLL cells confers markedly heightened sensitivity to 17-AAG or 17-DMAG, suggesting that these or other Hsp90 inhibitors could be valuable therapeutically in patients with aggressive CLL.

Progressive limitation of occular motility, accompanied by ptosis but usually without diplopia, occurs in many pathologic states, including mitochondrial diseases. A case with chronic progressive external ophthalmoplegia with onset during childhood, associated with proximal myopathy and dysphasia is presented. The muscle biopsy showed a myopathic pattern and abnormal subsarcolemmal mitochondrial deposits. Muscle biopsy for important in the correct diagnosis of this entity.