Management of cataract surgery in Lowe syndrome

INTRODUCTION

The Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare systemic disorder which involves several organ systems such as the eyes, the central nervous system and the kidneys

. The prevalence is estimated at 1 in 500 000 children

. It is an X-linked recessive disorder

,showing a key mutation in the

gene. This gene encodes for the enzyme OCRL-1, which is essential for cell functions such as protein trafficking, signaling and actin cytoskeleton polymerization. Dysfunction of this enzyme leads to an accumulation of the substrate phosphatidylinositol-4.5-biphosphate and impairs the intracellular pathways

. Upon birth, Lowe syndrome should be suspected if children show bilateral dense congenital cataract and infantile congenital hypotonia. Furthermore, a positive family history of male relatives is highly indicative. The definite diagnosis is then established on the results of the physical exam findings,laboratory findings and molecular genetic testing.Nervous system abnormalities, already present at birth, show severe central hypotonia and loss of the deep tendon reflexes which may complicate the vital functions (breathing) at birth.Hypotonia can slowly improve with age, but normal motor function and strength will not be achieved. Also, mental retardation is found in the majority of patients and many will develop maladaptive behaviors such as temper tantrums or irritability as well as seizures or febrile convulsions

.

最后一個(gè)夜晚，試圖再次撥打她的電話。這一次終于撥通，她清晰的聲音平淡自若，一如往昔，沒有任何情緒流露。只是說剛剛從森林里出來，在當(dāng)?shù)馗浇囊粋€(gè)小鎮(zhèn)里看病。身體一直不太舒服。

Kidney dysfunction may not be present at birth but rather develop during the first few months of life. Typically, a proximal renal tubular dysfunction of the Fanconi type is found in these patients, which include low molecular-weight proteinuria, aminoaciduria, bicarbonate and potassium wasting,renal tubular acidosis and proteinuria. Chronic renal failure slowly develops due to glomerulosclerosis associated with chronic tubular injury between the second and fourth decade of life

.

Congenital cataract will initially present as bilateral dens lens opacities during physical examination of the newborn

. Next to the congenital cataract, ophthalmic abnormalities include congenital glaucoma, nystagmus and keloids. Glaucoma is found in about 50% of patients

. Therefore, also typical glaucomatous changes such as corneal haze, increased corneal diameter or buphthalmos combined with lens opacities should be suspicious for Lowe syndrome.

Ophthalmic Evaluation The mean age of the children at diagnosis of congenital cataract was 4.07±3.26wk (1-8wk).Lens surgery was performed at the age of 8.98±3.58wk (3-12wk). The mean follow-up was 4.80±5.32y (1.11 to 15.91y).In all children a lensectomy combined with posterior capsulotomy and an anterior vitrectomy was performed. No IOL was implanted at the initial procedure as well as during the followup. Evaluation of the eye characteristics showed a mean eye length, the corneal diameter and the IOP of 17.16±2.01,10.38±0.41, and 10.63±1.49 mm Hg, respectively. In one eye of one child an iris bleeding developed during cataract surgery,whereas no intraoperative complication developed in the remaining eleven eyes (Table 2).

Ophthalmologists often examine babies only a few weeks of age, since parents or pediatricians found bilateral lens opacities. Prompt cataract removal is necessary to allow visual development. Therefore, a good cooperation between ophthalmologists and pediatricians is essential for the initial diagnosis and subsequently treatment and supportive therapy in these patients.

In this study, we evaluated the initial diagnose process, surgical treatment and the postoperative functional development and complications of children with Lowe syndrome.

SUBJECTS AND METHODS

將工程前后海域潮流特征流場分布繪于圖4，分析可知：工程海域的潮流周期為12 h，為典型的半日潮。工程海域潮流運(yùn)動(dòng)受風(fēng)向以及近岸輻射狀沙洲地形綜合影響，其中，南、中、北三個(gè)水道的潮流分布呈橢圓狀，潮流流向受南北兩側(cè)沙洲引導(dǎo)，與深槽方向趨近，且流向受潮汐影響，呈往復(fù)流特征。潮流傳遞呈典型駐波狀態(tài)。

Bilateral simultaneous cataract surgery was performed under general anesthesia in all cases.

華彩的背后，是鮮為人知的付出。但問起演戲的艱辛，趙多娜不愿多說，別看她在戲里扮演了各種類型的角色，生活中的她，其實(shí)很安靜，從不拿拍戲的辛苦大肆宣揚(yáng)?！爸灰俏艺J(rèn)定的事情，我都會(huì)很堅(jiān)持，甚至有點(diǎn)固執(zhí)。就拿演戲來說，我很享受拍戲的過程，拿它當(dāng)一輩子的事業(yè)來做?？赡苡袝r(shí)候家人朋友會(huì)有一些其它建議，比如女孩子要早點(diǎn)結(jié)婚生子，可以轉(zhuǎn)做一些幕后工作等等，但我還是會(huì)堅(jiān)持自己的信念?！壁w多娜篤定地說。

Five boys were born at the gestational week 37 to 39, whereas one child was born premature at week 26

and had to be treated at the NICU. The mean birth weight was 2865.17±1007.38 gram (Table 1). In two children a congenital infection was found, whereof in one child an endocarditis and in the other sepsis. At pediatric examination, cerebral hypotonia was observed in all children. Renal changes varied within the study population. One child showed no renal changes, whereas renal calcinosis was found in three children, isolated proteinuria and hydronephrosis in one child each.

測試溫度保持常溫不變,依次增加980 nm泵浦功率,stokes階數(shù)也隨之增加,當(dāng)泵浦功率增加到600 mW時(shí),產(chǎn)生了如圖4所示的30階穩(wěn)定stokes線。

Different approaches in the management of pediatric cataract surgery are discussed in literature. Especially, the time point of cataract extraction for uni- and bilateral congenital cataract is discussed with regard to the functional outcome and avoiding postoperative complications

. In Lowe syndrome, both eyes are predominantly affected, making surgery on both eyes necessary.

RESULTS

This study included twelve eyes of six male children. In all children initial diagnosis was made clinically, whereof in three boys at the Ophthalmic Department and in one child at the Neonatology Intensive Care Unit (NICU). Genetic testing in all children confirmed the diagnosis of Lowe syndrome.

During surgery, a complete ophthalmologic examination including ultrasound B-scans (Ocuscan; Alcon Laboratories,Fortworth, Texas, USA) for evaluation of axial eye length and the posterior segment, measurement of intraocular pressure(IOP) and keratometry was performed. Cataract surgery was performed through the aspiration of the soft lens material with a bimanual irrigation-aspiration system. Afterwards, a posterior capsulotomy was done using either a bent needle or the vitrector. All children remained aphakic and glass or contact lenses were prescribed for postoperative visual rehabilitation.Outcome measures included descriptive data (age and gender), information on the cerebral and renal pathologies and the surgical procedure. Anesthesia outcomes, composed of duration of surgery and anesthesia (measured in minutes,min)—that is, total anesthesia time (intubation to extubation),extubation time (time between the end of surgery and extubation), time in the recovery room, and events of oxygen decrease (below 93% was regarded as severe hypoxia)—were recorded. The type intra- (iris bleeding, expulsive bleeding,posterior capsule rupture, intraocular lens (IOL) problems,iris dislocation) and postoperative complications [glaucoma,visual axis obscuration (VAO), synechia, retinal detachment,endophthalmitis or enucleation] were analyzed as well as the number of surgical re-treatments.

Ethical Approval This retrospective, case series was performed at the Department of Ophthalmology, Vienna.Ethics approval for retrospective chart review and analysis was obtained from the local ethics committee (EK: 1116/2019)and adhered to the tenets of the Declaration of Helsinki.Medical records of patients aged 0 to 18y with genetically verified Lowe syndrome who received cataract extraction were included to the study. The Ethics Committee did not ask for informed consent as this was a retrospective chart review.

The initial approach is the cataract removal under general anesthesia. During surgery a complete ophthalmic examination will be carried out including assessment for glaucomatous changes

.

The mean time for cataract surgery per eye was 35.83±8.86min,whereas the total time of surgery was 153.33±22.11min. Four children received an endotracheal tube, whereas two children a larynx mask. The mean extubation time and duration at recovery room was 42.33±22.60min and 130.00±64.37min,respectively. During surgery, a decrease of oxygen saturationbelow 93% was found in only one child. Additionally,no serious complications such as asphyxia, malignant hyperthermia, cardiac and respiratory arrest or seizures were observed during surgery. One child, who showed a short period of insecure respiratory function during extubation,was transferred intubated to the recovery room. Extubation was then performed without complications. Afterwards, this child was brought to the pediatric intensive care unit for postoperative observation. All children left the hospital one to three days after cataract surgery, except the child who was born prematurely. This child remained at the hospital for another 43d because of the need for neonatal care.

CEFTIN在急性細(xì)菌性上頜竇炎患者，用于治療由產(chǎn)β‐內(nèi)酰胺酶的流感嗜血桿菌或卡他莫拉菌所致鼻竇感染的有效性尚未確定，因?yàn)榕R床試驗(yàn)中這些分離菌數(shù)量不足［見臨床研究（14.1）］。

During the postoperative follow-up, nystagmus was found in all children. Strabismus was seen in five children, whereof in four children an esotropia and in one child an exotropia. One child developed a VAO during the postoperative follow-up.

Secondary glaucoma developed in five eyes of three children.The maximum IOP was 21.75±10.49 mm Hg (10 to 40 mm Hg)during the follow-up. A trabeculectomy was performed in both eyes of one child four months after lens extraction, whereas a removal of synechia and an iridectomy in one eye of one child one year after lens surgery. In the third child, glaucoma was successfully controlled using topical IOP medication (betablocker).

At the last follow-up, the children showed a visual function of 0.61±0.88 logMAR (0.1-0.4 Snellen). No further surgical interventions were performed during the postoperative followup. However, in two children an examination under general anesthesia was performed for evaluation of glaucomatous changes.

During the follow-up one child, who was born prematurely and showed bronchopulmonary dysplasia, died at the age of 14.93mo due to recurrent respiratory infections (13.2mo after the cataract surgery).

DISCUSSION

From an ophthalmological point of view, Lowe syndrome is mainly characterized by bilateral cataract followed by infantile glaucoma and corneal kelloids. In addition, various diseases of the cerebrovascular system such as generalized hypotonia or intellectual impairment as well as renal changes such as renal tubular sclerosis or proteinuria have been described

. The primary goal is established by the diagnosis

genetic testing in order to initiate adequate treatment and early intervention.In the ophthalmological field, cataract surgery and glaucoma management are the first priorities.

Furthermore, four of the six children presented to the Ophthalmology Department within the first two weeks of life.Children with congenital cataract present very early to eye doctors, which demonstrates the special role of ophthalmologists in the screening process of newborns. Bilateral cataract requires,in general, further pediatric examination, since congenital infections (such as toxoplasmosis, rubella, cytomegalovirus,herpes simplex or other infections,

, syphilis,Varicella-Zoster, HIV or Parvo-B19) or drug exposures have to be ruled out

. Subsequently, a good cooperation and network between ophthalmologists and pediatricians is essential for the timely diagnosis and treatment, especially, if Lowe syndrome is suspected.

Within the demographic results we saw a male predomination of the study population, which is also described in the literature

. About 95% of heterozygous females show specific cortical lens opacities in the shape of snowflakes already during the teenage years. However, cataract surgery is rarely required at a young age in female carriers

.

Statistical Analysis Microsoft Excel

2010 was used for collecting patients’ data, which was then converted to SPSS

version 20 (SPSS, Inc., Chicago, IL, USA) for statistical analysis. Nominal data is given as numbers or percentages,whereas continuous data is given as means±standard deviations(SDs).

At our clinic, bilateral cataracts are treated in one session of general anesthesia but with special care taken

new equipment (two separate phako sets) or change of clothes and gloves. This has the advantage that the children do not need another operation and therefore the total anesthesia time can be significantly reduced. In a retrospective analysis of anesthesia times in pediatric cataract surgery, surgery times per eye and the total anesthesia time were similar to our study results, only extubation time and recovery room time were prolonged

.This may be due to the fact that the anesthetists knew about the suspected diagnosis Lowe syndrome, and therefore general anesthesia was performed more cautiously, or due to the fact that the children took longer to wake up and breathe on their own due to cerebral hypotension or delayed excretion due to the underlying renal pathologies. However, the children could be discharged from the inpatient area relatively quickly after the operation (on average 1-3d). Furthermore, the children did not experience any complications during anesthesia. One child showed prolonged weaning during extubation, but the tube could be removed in the recovery room without further complications.

2)由DSM生成的等高線中含有大量自閉合微短等高線，其來源可分為兩種：一種出現(xiàn)在植被和建筑物等地物表面，不屬于地形，這是錯(cuò)誤的等高線；……