Hereditary hyperferritinemia cataract syndrome: ocular, genetic, and biochemical findings

PURPOSE: To describe the cataract morphology and genetic and biochemical findings in a four-generation family with hereditary hyperferritinemia cataract syndrome (HHCS). METHODS: Family members of the proband with HHCS were investigated. DNA sequencing was carried out to identify the iron responsive element (IRE) of the L-ferritin gene in affected and non-affected family members. Molecular modeling allowed prediction of the structure of the mutant IRE in affected cases. Serum ferritin and transferrin saturation were determined using standard methods. All family members underwent slit lamp examination by an ophthalmologist to document presence of cataract or lens status. Cataract morphology was documented where present. RESULTS: This family with HHCS had the genetic heterozygous mutation G32C in the IRE of the L-ferritin mRNA. Lens opacities were detectable in young members of the family, and morphology of cataracts was consistent with previous reports. Biochemical testing demonstrated high serum ferritin levels in affected individuals. CONCLUSIONS: The morphology of cataracts in HHCS seems to be similar in all cases. In the heterozygous G32C mutation, the age at onset of cataracts is very early. Greater awareness of this condition among ophthalmologists will lead to effective family counseling of those affected, by genetic testing or simple biochemical tests. Serum ferritin levels can be effectively used to screen for this condition in suspected families.     

Hereditary hyperferritinemia syndrome and cataract

Hereditary hyperferritinemia cataract is a recently described autosomal dominant syndrome, characterized by bilateral cataracts and elevated level of serum ferritin. PATIENTS: Three members of a family were investigated for cataract and hyperferritinemia. A 30-year-old woman had elevated serum ferritin levels and bilateral cataracts. She was treated for hemochromatosis, but serum iron and transferrin saturation were normal. Her two sons, nine and five years old, also had a high ferritin level and bilateral cataracts. RESULTS: The ferritin level was 1200 micrograms/L in the woman's serum, and respectively, 974 and 965 micrograms/L in the two boys' serum. The mother had a visual acuity of 8/10 in the right eye and 5/10 in the left eye. The cataract comprised fine crystalline cortical opacities, extending axially. The two sons had 7 to 8/10 in both eyes. No other ophthalmic abnormality was noted. These patients were heterozygous for a 16 bp deletion on the L-ferritin gene. DISCUSSION: Ferritin is an iron storage ubiquitous protein present in every cell. In hyperferritinemia cataract syndrome, serum iron and transferrin saturation are normal, and the elevated serum ferritin level is the consequence of an autosomal dominant disorder. The cataract is made up of the accumulation of small opacities disposed radially and more numerous on the outside edges, with relatively good visual acuity. The size of the cataract seems to be correlated to the serum ferritin level. In hemochromatosis, hyperferritinemia is related to increased iron stores and is not associated with cataracts.     

Implantable contact lens for moderate to high myopia: relationship of vaulting to cataract formation

PURPOSE: To study cataract formation in eyes with an implantable contact lens (ICL) used for moderate to high myopia. SETTING: University Eye Hospital, Lausanne, Switzerland. METHODS: An ICL (model V3 or V4, Staar Surgical AG) was implanted in 75 eyes. Three months after surgery and again at the last follow-up examination, the transparency of the crystalline lens was assessed on transilluminated photographs and the vaulting of the ICL over the crystalline lens was evaluated. Central vaulting was measured precisely on digitized photographs taken with a 75 SL Zeiss slitlamp camera, while peripheral vaulting was estimated on photographs obtained with a Scheimpflug camera. The minimum follow-up was 12 months; the mean was 21.8 months. RESULTS: At the last follow-up, 20 of the 75 eyes (27%) had an ICL-induced anterior subcapsular cataract (ASCC). The number of cataracts increased with the duration of the follow-up. Cataracts developed more commonly in older patients than in younger patients. All 20 cataracts occurred when the central vaulting was equal to or less than 0.09 mm. In 26 eyes with the same range of vaulting (among which 11 had no vaulting), the lenses were clear at the last visit. The 20 patients with cataract and the 26 patients with clear lenses matched in age and duration of follow-up but not in myopia. No touch between the ICL and the crystalline lens was encountered when the central vaulting was equal to or greater than 0.15 mm. Vaulting showed a slight decrease over time. No statistically significant difference in vaulting was found between models V3 and V4. CONCLUSION: Central and/or peripheral contact between the ICL and the crystalline lens may be responsible for the high incidence of ASCC formation in this study. Central vaulting greater than 0.09 mm appears to protect the crystalline lens from cataract formation. However, we recommend aiming for higher central vaulting (0.15 mm) to avoid contact between the ICL and the crystalline lens. This should be attainable by implanting longer ICLs.     

Sugar metabolism in the crystalline lens

Research on the sugar metabolism of the crystalline lens, past and present, is reviewed. The chief energy source in the lens is the Embden-Meyerhof pathway; respiration and oxidative phosphorylation become more important as the lens ages. The function of the α-glycerophosphate cycle is not fully understood. The mechanisms involved in cataract formation, including those of hypoglycemic cataract and osmotic cataracts, are discussed. Sugar cataracts can be delayed or prevented with such aldose reductase inhibitors as flavonoids. By inhibiting aldose reductase, the formation and accumulation of sugar alcohols is stopped. This approach may be useful as a medical therapy for human diabetic senile cataracts.     

Hereditary hyperferritinemia-cataract syndrome.

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a recently recognized syndrome characterized by dominantly inherited, early-onset cataracts and elevated serum ferritin. The opacities are caused by elevated ferritin protein within the crystalline lens and usually become symptomatic in the second to fourth decade of life. Routine laboratory tests can establish this diagnosis. We report two unrelated cases that presented in the United States.     

Central choroidal thickness in children and adolescents with anxiety disorders: enhanced depth imaging optical coherence tomography findings

AIM: To measure the central choroidal thickness (ChT) in children and adolescents with anxiety disorders. METHODS: Totally 41 anxiety patients (8-16y) and 35 healthy controls (age-matched) were evaluated. Complete ophthalmic examination was performed. Inclusion criteria were best corrected visual acuity ≥20/20, normal intraocular pressure (IOP; 10-21 mm Hg), and no systemic or ocular diseases according to history. The diagnosis of psychiatric disorders was determined using Schedule for Affective Disorders and Schizophrenia for School Aged Children Present-Lifetime Version (K-SADS-PL). Enhanced depth imaging optical coherence tomography (EDI-OCT) was used to measure the central ChT. RESULTS: The mean age was 12.18±3.24y in the patient group and 12.86±3.15y in the control group. Age and gender distribution of the two groups was similar. Central ChT mean value was 353.26±31.9 μm in anxiety patients while 318.75±60.9 μm in the control group. Mean central ChT was statistically significantly higher in the children and adolescents with anxiety disorders than healthy controls (P=0.002). CONCLUSION: The children and adolescents with anxiety disorders have significantly thicker central ChT than controls. In the larger sample, longitudinal studies will contribute to the use of choroidal differences as a clinical marker for monitoring anxiety disorders.     

Anterior subcapsular plaque cataract in hyperornithinaemia gyrate atrophy--a case report.

Hyperornithinaemia gyrate atrophy (HOGA) is a rare autosomal recessive disorder in which chorioretinal degeneration occurs with cataracts, myopia, and hyperornithinaemia. We report the case of an 18-year-old female who presented with the typical features of HOGA, including posterior subcapsular cataracts and elevated plasma ornithine. She later developed distorted vision in both eyes owing to wrinkling of the anterior lens capsules. Histological examination following lens extraction showed the wrinkling was caused by focal distortion from capsular fibrosis (anterior subcapsular plaque cataract). This specific lens change has not been linked previously with HOGA.     

A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family

AIM: To determine the prevalence and associations of non-retinopathy ocular conditions among older Australian adults with diabetes. METHODS: Multistage random-cluster sampling was used to select 3098 non-indigenous Australians aged 50y or older (46.4% male) and 1738 indigenous Australians aged 40y or older (41.1% male) from all levels of geographic remoteness in Australia. Participants underwent a standardised questionnaire to ascertain diabetes history, and a clinical examination to identify eye disease. We determined the prevalence of uncorrected refractive error, visually significant cataract, cataract surgery, age-related macular degeneration, glaucoma, ocular hypertension, retinal vein occlusion and epiretinal membrane among those with and without self-reported diabetes. RESULTS: Participants with self-reported diabetes had a higher prevalence of cataract surgery than those without diabetes (28.8% vs 16.9%, OR 1.78, 95%CI: 1.35-2.34 among non-indigenous Australians, and 11.3% vs 5.2%, OR 1.62, 95%CI: 1.22-2.14 among indigenous Australians). Diabetic retinopathy (DR) increased the odds of cataract surgery among self-reported diabetic indigenous and non-indigenous Australians (OR 1.89, P=0.004 and OR 2.33, P<0.001 respectively). Having diabetes for ≥20y and having vision-threatening DR increased the odds of cataract surgery among indigenous Australians with diabetes (OR 3.73, P=0.001 and 7.58, P<0.001, respectively). CONCLUSION: Most non-retinopathy ocular conditions are not associated with self-reported diabetes. However, to account for Australia’s worsening diabetes epidemic, interventions to reduce the impact of diabetes-related blindness should include increased cataract surgery services.     

Protein oxidation and lens opacity in humans

PURPOSE: Oxidative damage to lens proteins is a major factor leading to cataract formation. It is of pathogenic importance to determine a threshold of protein oxidation over which opacification of the lens takes place. METHODS: Sixty-two lenses extracted from patients affected by idiopathic senile, diabetic, or myopic cataract were studied. Clear lenses were obtained from subjects undergoing enucleation (n = 10) or vitrectomy for giant retinal tears (n = 9), and were age- and sex-matched to those with cataract. The content of carbonyls and sulfhydryls (P-SH) in proteins in the lens was assessed using spectrophotometric assay. RESULTS: An age-associated inverse relation (P < 0.01) was noted in the content of P-SH, the concentrations of which were also inversely related (P < 0.03) to the content of protein carbonyls. These changes were more pronounced in cataracts than in clear lenses and in diabetic and myopic cataracts when compared with senile cataracts. The drop of P-SH concentration occurred earlier in diabetic and in myopic cataracts than in senile cataracts. The accumulation of protein carbonyls > 2 nmol/mg protein and the decrease of P-SH below 12 to 10 nmol/mg protein were always accompanied by lens opacification. CONCLUSIONS: Idiopathic senile, diabetic, and myopic cataractogenesis appear to be dependent on oxidative damage to lens proteins. This damage occurs earlier in myopic and diabetic patients. Values of P-SH below and protein carbonyls above their specific threshold were found to be predictive for the presence of cataract. Because increased oxidation was observed in clear lenses removed from myopic and diabetic subjects, oxidation may be involved in the pathogenesis of these forms of human cataract.     

Cortical and subcapsular cataracts: significance of physical forces

Cortical cataracts usually begin with either sharp limited clear fluid clefts, resulting in opaque spokes, or clear lamellar separations, resulting in cuneiform opacities. They do not commence prior to 45 years of age. From this age on an increase in lens nuclei hardening can be detected. Therefore, during disaccommodation in older lenses, mechanical shear stresses must develop between the soft remaining cortices and the harder nuclei. These shear stresses are significant regarding the different cortical ruptures in predisposed lenses: in a privileged radial direction (according to zonular traction) of the sharp limited cortical spokes, or in parallel microridges at the commencement of lamellar separations, as observed when a rubber surface slides against a harder object. In pure cortical cataracts the ion pump (K+ > Na+) and investigated metabolic parameters remain largely intact. Therefore, it is not surprising that, in contrast to subcapsular cataracts, subcapsular opacities do not occur. Subcapsular cataracts are known to be caused by a variety of factors: aging, diabetes, corticosteroids, iridocyclitis, or X-ray, among many others. In contrast to cortical cataracts, subcapsular cataracts were found to be closely associated with ion pump damage (Na+ > K+) and a variety of metabolic activity alterations. In subcapsular cataracts passive fluids (from the vitreous and camera anterior) enter externally through the lens capsule. This initially forms numerous free clear, secondary grey, subcapsular fluid vacuoles. If the ion pump (metabolic barrier) is more severely damaged fluids may also enter the lens nucleus (secondary grey nuclear cataract), which rarely results in intumescent cataract. In cortical and subcapsular cataracts and lens perforations the main cause of grey opalescence appears to be the result of lens proteins (water-soluble crystalline) coming into direct contact with free fluids (water). In cortical cataracts this happens in the area of sharp limited mechanical cortical ruptures (fluid clefts), and in subcapsular cataracts during passive, external fluid entry, resulting in subcapsular fluid vacuoles and opacities, and also later grey-white nuclear opacities. The importance of water contact with water-soluble lens crystallines in behalf of light scattering and turbidness also has been investigated experimentally.     

Changes in cytoskeletal proteins in childhood cataract lenses

Purpose: Approximately 50% of congenital and childhood cataracts seen in the clinic is of undetermined origin. Biochemical analysis of the cataracts is rare. This study analyzes lens proteins to determine the mechanism of congenital and childhood cataracts. Method: We analyzed the lens proteins from 10 young patients after cataract operations, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), densitometry analysis, and Western immunoblotting.Results: Densitometry of separated proteins showed a decrease in the high molecular protein bands of posterior subcapsular cataract (PSC). Specifically, spectrin (235 kDa), filensin (100 kDa), and vimentin (57 kDa) were absent from the SDS-PAGE of PSC. Increases in filensin and vimentin were observed in a Christmas tree cataract and lamellar cataracts. Western immunoblots confirmed the densitometry of SDS-PAGE.Conclusion: These results suggest that changes in cytoskeletal proteins may contribute to congenital and childhood cataracts.     

Rapid onset phacolysis.

BACKGROUND: Phacolysis involves the breakdown of a hypermature cataract, causing an antigenic reaction to the lens proteins released into the anterior chamber with subsequent inflammation. To date, the time it takes for a crystalline lens to reach hypermaturity and induce a phacolytic response has never been clearly detailed. It is believed that cataract maturation is a slow process. The process by which the lens proteins begin to leak is thought by many to be similarly slow. However, the immune-related inflammatory process that develops when the lens proteins begin to leak may be quite rapid. It may be an error to consider this aspect of the phacolytic process to be slow. METHODS: We present a case with a clear, timed delineation of the phacolytic process. A mature cataract became hypermature with subsequent phacolysis and inflammatory pressure rise over the course of 17 days. It appears that this is the first published account of the time involved in the development of phacolysis and, we believe, the fastest onset of the process. CONCLUSION: While cataract maturation is generally considered to be a slow, insidious process, it should be recognized that the phacolytic process might not be slow. Once a lens reaches hypermaturity, phacolysis could occur quite rapidly over the course of several days. This case could be an important consideration in management of the removal of advanced cataracts. This case may be the shortest reported time from diagnosis of a mature cataract to the development of inflammatory phacolysis and secondary glaucoma, occurring over a period of only 17 days.     

Changes in cytoskeletal proteins in childhood cataract lenses]

PURPOSE: Approximately 50% of congenital and childhood cataract seen in the clinic is of undetermined origin. Biochemical analysis of the cataracts is rare. This study analyzes lens proteins to determine the mechanism of congenital and childhood cataracts. METHOD: We analyzed the lens proteins from 10 young patients after cataract operations, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), densitometry analysis, and western immunoblotting. RESULTS: Densitometry of separated proteins showed a decrease in the high molecular protein bands of posterior subcapsular cataract (PSC). Specifically, spectrin (235 kDa), filensin (100 kDa), and vimentin (57 kDa) were absent from the SDS-PAGE of PSC. Increases in filensin and vimentin were observed in a Christmas tree cataract and lamellar cataracts. Western immunoblots confirmed the densitometry of SDS-PAGE. CONCLUSION: These results suggest that changes in cytoskeletal proteins may contribute to congenital and childhood cataract.     

年龄相关性白内障患者晶状体倾斜和偏心及其影响因素——基于CASIA2的研究北大核心

目的运用新型眼前节光学相干断层成像仪CASIA2观察年龄相关性白内障患者晶状体倾斜及偏心的情况,并分析其影响因素。方法本研究为横断面研究。选取2020年4月至2021年5月于天津医科大学眼科医院就诊并接受白内障手术的310例(310眼)年龄相关性白内障患者。运用CASIA2的晶状体分析模式测量晶状体倾斜与偏心,并对其作描述性分析。采用单因素线性回归分析及多因素线性回归分析患者晶状体倾斜及偏心与影响因素的关系。纳入分析的影响因素包括:年龄、糖尿病史、眼轴长度(AL)、中央角膜厚度(CCT)、房水深度(AD)、晶状体厚度(LT)、Alpha角及Kappa角。结果纳入310例(310眼)白内障患者,年龄(68.8±8.5)岁,晶状体倾斜度为(4.97±1.59)°,偏心量为(0.21±0.12)mm。晶状体倾斜方向为颞下方,偏心方向为颞侧。其中,晶状体倾斜度>7°者占10.3%,偏心量>0.4 mm者占7.7%。单因素线性回归分析结果显示,晶状体倾斜度与晶状体偏心量、年龄、AL、Alpha角及Kappa角均有相关性(均为P<0.05);而晶状体倾斜度与糖尿病史、CCT、AD、LT均无相关性(均为P>0.05)。晶状体偏心量与年龄、倾斜度、Alpha角及Kappa角均有相关性(均为P<0.05);而晶状体偏心量与糖尿病史、AL、CCT、AD、LT均无相关性(均为P>0.05)。多因素线性回归分析结果显示,晶状体倾斜度与晶状体偏心量、AL及Alpha角均有相关性(均为P<0.05);而晶状体倾斜度与年龄、糖尿病史、CCT、AD、LT及Kappa角均无相关性(均为P>0.05)。晶状体偏心量与倾斜度及AL均有相关性(均为P<0.05);而晶状体偏心量与年龄、糖尿病史、CCT、AD、LT、Alpha角及Kappa角均无相关性(均为P>0.05)。结论年龄相关性白内障患者晶状体朝颞下倾斜、向颞侧偏心。在晶状体倾斜度较大的眼中,偏心程度更重。晶状体在短AL眼中及Alpha角大的眼中倾斜程度更重。白内障术前应综合考虑晶状体倾斜、偏心情况及AL、Alpha角等影响因素,合理选择功能型人工晶状体。     

Automated irrigation/aspiration before phacoemulsification in eyes with white cataracts.

BACKGROUND AND OBJECTIVE: A white mature cataract still presents a significant challenge for the cataract surgeon. Because of the reduced visibility and increased intracapsular pressure in such cases, it is difficult to consistently achieve controlled continuous curvilinear capsulorhexis. Several simple procedures for treatment of eyes with white mature cataract are described. PATIENTS AND METHODS: Seven consecutive patients (7 eyes) with white cataracts were enrolled for cataract surgery from July 2002 to February 2003. A small, central anterior capsular opening was created after carefully filling the anterior chamber with viscoelastic agents. Automated irrigation/aspiration by lowering of a connected bottle of balanced salt solution was used to aspirate the liquefied milky lens contents and decrease intracapsular pressure. RESULTS: All patients obtained controlled capsulorhexis, safe cataract phacoemulsification, and in-the-bag intraocular lens implantation. CONCLUSION: Automated irrigation/aspiration before phacoemulsification is safe and effective for eyes with white cataracts.     

Lensectomy-vitrectomy indications and techniques in cataract surgery

Lensectomy-vitrectomy is the removal of the crystalline lens through a transscleral retrociliary incision (usually the pars plana) under clinical conditions in which the vitreous gel has to be partially or totally removed. It was designed in the early 1970s at the onset of modern vitreous surgery. The vitreous cutter was used to remove the lens and the vitreous (lensectomy as vitrectomy). With the development of small incision cataract surgery, foldable IOL, the term lensectomy-vitrectomy also applies to separate incisions in one procedure combining lens and vitreous surgery. With this in mind, it covers several very different situations from neonatal congenital cataracts to adult or senile-associated diseases. This type of surgery is widely accepted, and the main controversy is about the consequences of neonatal surgery and the age of IOL implantation in uni- or bilateral congenital cataracts. My personal work with laser flare and cellmetry demonstrates that pars plana vitrectomy alone creates very little trauma to the blood-aqueous barrier, as can be checked by the anterior chamber level of proteins (ie, flare). The postoperative flare in pars plana vitrectomy alone is very close to the preoperative level. Therefore, the association of pars plana vitrectomy and lens surgery should not be more traumatizing to the eye than lens surgery alone. This review will first report the consequences of neonatal lensectomy-vitrectomy to the eye. Subsequent indications for surgery and implantation will be discussed as well as special indications and complications in congenital cataracts, dislocated nucleus in cataract operation, cataract and associated vitreoretinal disorders in diabetes, and giant retinal tears and removal of the lens during vitrectomy.     

Pyramidal anterior polar cataracts

OBJECTIVE: To document clinical features and subsequent management of pyramidal anterior polar cataracts in children. DESIGN: Retrospective, noncomparative case series and clinicopathologic correlation. PARTICIPANTS: Fifteen patients who presented to the pediatric ophthalmology clinic. INTERVENTION: All patients underwent measurement of visual acuity, assessment of ocular motility, examination of the anterior and posterior segments, and cycloplegic refraction. Amblyopia treatment was instituted when appropriate. When visual impairment occurred from cataract progression or amblyopia or both, cataract removal with or without lens implantation was performed. After surgery, correction of refractive error and treatment of amblyopia were instituted. Several pyramidal opacities were retrieved during cataract extraction and examined by light and electron microscopy. MAIN OUTCOME MEASURES: Visual acuity at initial presentation, size of lens opacity before surgery, amblyopia status, most recent visual acuity after cataract extraction, and histologic examination of lens opacity. RESULTS: Nine children had bilateral and six had unilateral pyramidal cataracts (24 eyes). There was no discernible inheritance pattern. Patients were followed for 27 months on average. Twenty of 24 eyes developed cortical opacification that extended significantly beyond the base of the pyramidal lesion. Nineteen eyes required cataract surgery: 10 eyes underwent lensectomy with anterior vitrectomy and 9 had extracapsular cataract extraction, 8 of which had insertion of a posterior chamber intraocular lens. Amblyopia was present or developed in all six patients with unilateral cataract and in eight of nine patients with bilateral cataract. Visual acuity in many eyes remained poor despite amblyopia therapy. The pyramidal opacities consisted of hyperplastic lens epithelium, which exhibited a loss of polarity and was surrounded by a collagenous matrix. CONCLUSIONS: Pyramidal anterior polar cataracts are present at birth and may represent a variant of anterior polar lens opacities. They may be unilateral or, if bilateral, they may be either symmetric or asymmetric. They consist of hyperplastic lens epithelium in a collagenous matrix. Patients with pyramidal cataracts are likely to develop amblyopia. This can result from either unilateral occurrence or asymmetry of bilateral opacities and is often worsened by surrounding cortical opacification. Many patients require cataract surgery. All infants and young children with anterior polar opacities showing this configuration should be followed for cataract progression and amblyopia.